Common parasitic Infections of GIT ( Infectious diarrhea)

Common parasitic Infections of GIT (Infectious diarrhea) Dr Muhammad Raza

Parasites Protozoa one cell Metazoa multi cells ↓ Cause diarrhea Platy-helminthes Flat worms Nema-helminthes Round worms • Rotaviruses • Norwalk viruses • S. aureus • Bacillus cereus • Clostridium perfringens • Giardialamblia Cestode Tape-worms Trematode Flukes Common causes of Infections of GIT

Infectious diarrheas Classified as • Non-inflammatory diarrhea: is a less severe illness, presenting as watery stools without blood, WBCs or occult blood. Patients are afebrile and without significant abdominal pain. Caused by: • Rotaviruses, • Norwalk viruses, • S. aureus, • Bacillus cereus, • Clostridium perfringens, and • Giardialamblia. • Inflammatory diarrhea: is a more severe illness, presenting as bloody diarrhea with large numbers of fecal leukocytes; patients are febrile and complain of severe abdominal pain. Caused by: invasive pathogens, including • Campylobacter jejuni, • Shigellaspecies, • non-typhoid Salmonella, • C. difficile, Shiga toxin or verotoxin—producing E coli (VTEC), and • Entamoebahistolytica.

Predisposing factors • Travel history • Compromised immune status, • Outbreaks of food-borne or water- borne illnesses, • Personal hygiene, and • Use of pharmacologic agents • Drugs

Management of patients with infectious diarrhea • 1. Initial management: focuses on the need for rehydration and correction of electrolyte disturbances as most cases are self-limited with no need of drug therapy • 2. Evaluate for further medical therapy, including the benefit of antimotilityand antisecretory drugs and antimicrobials. • 3. Most patients with non-inflammatory diarrhearequire only supportive therapy, while some patients with inflammatory diarrheamay benefit from antimicrobial therapy. • -Rehydration Therapy: is based on the degree of dehydration. • S/S ofmild to moderate dehydrationinclude decreased skin turgor, dry skin, axillae & mucous membranes, thirst, and dizziness due to postural hypotension.

Based on the greater efficacy of reduced osmolarity ORS solution, especially for children with acute, non-cholera diarrhoea, WHO and UNICEF now recommend the following formulation in place of the previously recommended standard ORS solution. • TTT: Oral rehydration solution recommended by WHO (Previously recommended) • Glucose 20 g/L --Sodium 90 mEq/L • Potassium 20 mEq/L --Chloride 35 mEq/L • Citrate 30 mEq/L and --WATER Q.S. 1L Source: A manual for physicians and other senior health workers (WHO)

ORS Solution • ORS solution provides sufficient water and electrolytes to correct the deficits associated with acute diarrhoea. • Potassium is provided to replace the large potassium losses associated with acute diarrhoea, especially in infants, thus preventing serious hypokalaemia. • Citrate is provided to prevent or correct base deficit acidosis. • Glucose is essential because, when it is absorbed, it promotes the absorption of sodium and water in the small intestine. This is true irrespective of the cause of the diarrhoea. • Without glucose, ORS solution would be ineffective.

Management of patients with infectious diarrhea • S/S ofsevere dehydration include cold clammy extremities, agitation and confusion due to decreased cerebral blood flow, hypotension, tachycardia, cyanosis, and low urine output (usually <15 ml/hr). • TTT: IV (Ringer’s lactate and normal saline to which potassium and bicarbonate may be added as necessary to replace electrolytes. • N.B. IV therapy is used in mild to moderate cases if unable to drink e.g. in presence of paralytic ileus.

Source: A manual for physicians and other senior health workers (WHO) Lactate is converted by the liver to bicarbonate, which is required for the correction of base-deficit acidosis

ORS solution salted drinks vegetable or chicken soup + salt. ORT at health facility Monitor progress of ORT Zinc supplement + Food. Monitor IV therapy for rehydration Supplement e other electrolytes looking symptoms.

Prevention • Measures to prevent the spread of enteropathogens • good personal hygiene and • proper handling, cooking, and storage of foods • Persons traveling to areas that have sub optimal sewage and water systems should follow the rule, “boil it, cook it, peel it, or forget it.” • In addition, vaccines to prevent typhoid fever are available.

Drug Therapy • 1. Antimotility agents:loperamide and "diphenoxylate/ atropine • MOA:symptomatic relief by reducing propulsive peristalsis, facilitating the absorption of intestinal contents & increasing anal sphincter tone. • 2. Adsorbents: like pectins, adsorb toxins, bacteria, and rotavirus and strengthen the mucosal barrier. • 3. Antisecretory and Others: e.g. bismuth subsalisylate, Polycarbophil, Attapulgite • Characters: insoluble in GIT, reduce stool frequency, has antimicrobial effect (bismuth) and antisecretory effect (salicylate). • 4. Antimicrobials • Advantages: • Decrease the duration of illness and the severity of illness. • Prevent invasive infection. • Prevent person-to-person transmission of pathogens. • Empiric antimicrobial therapy without additional laboratory testing may be indicated in the following settings: • Severe illness e.g. • 1) Suspected bacterial diarrhea fever and stools positive for fecal leukocytes or occult blood. • 2) Persistent diarrhea for >2 weeks and if Giardia is suspected. • Travelers’ diarrhea. • Patients with conditions that compromise normal enteric defenses. • Immune-compromised patients. • To treat extra-intestinal complications of enteric infection, such as bacteremia and osteomyelitis.

Drug Therapy • 1. Antimotility agents: • loperamide (Opiate analogue) and Codeine (Opium alkaloid) • diphenoxylate/ atropine (lomotil) • MOA: symptomatic relief by • reducing propulsive peristalsis, • facilitating the absorption of intestinal contents & • increasing anal sphincter tone. • Advantages of loperamide over diphenoxylate/atropine: • Lower risk for side effects as it does not cross BBB. • Diphenoxylate/atropine may cause • drowsiness, • dizziness, • dry mouth, and • urinary retention. • Contraindications: patients with febrile dysentery or in children due to the potential to prolong the illness the potential for harmful effects, including ileus.

Drug Therapy • 2. Adsorbents: like pectins will adsorb toxins, bacteria, and rotavirus and strengthen the mucosal barrier. • Kaolin-pectin mixture-5.7 g kaolin + 130.2 mg pectin/30 mL- 30-120 mL after each loose stool • Kaopectate mixture (like attapulgite) • Polycarbophil-500 mg/tablet- Chew 2 tablets four times daily or after each loose stool; do not exceed 12 tablets/day • Synth. Hydrophilic polyacrylic resin absorbs 60X water of its wt. • Attapulgite-750 mg/15 mL (750 mg/tablet)- 1200-1500 mg after each loose bowel movement or every 2 hours; up to 9000 mg/day • Natural AlMg silicate, absorb 8X water of its wt.

Drug Therapy • 3. Antisecretory and Others: e.g. • bismuth subsalisylate • Characters: insoluble in GIT, reduce stool frequency, has antimicrobial effect (bismuth) and antisecretory effect (salicylate). It is relatively safe and may cause blackening of tongue and stool • Sulfasalazine---low solubility, local antiinflammatory effect, inhibit PG synthesis, decrease mucosal secretion→ relief in ulcerative colitis & IBD → Reduce number of stools, abdominal cramps • Enzymes (lactase)- 1250 neutral lactase units/4 drops (or 3300 FCC lactase units per tablet) → 3-4 drops taken with milk or dairy product ( or1 or 2 tablets as above) • Bacterial replacement (Lactobacillus acidophilus, Lactobacillus bulgaricus) → 2 tablets or 1 granule packet 3 to 4 times daily; give with milk, juice, or water

Drug Therapy • 4. Antimicrobials • Advantages: • Decrease the duration of illness and the severity of illness. • Prevent invasive infection. • Prevent person-to-person transmission of pathogens. Trimethoprirn-sulfamethoxazolecombination (Cotrimoxazole) has been used extensively for the treatment of enteric infections due to the following: • Synergism of activity between the two drugs • Wider antibacterial range • The combination is bactericidal for some organisms rather than bacteriostatic • Easy administration, relative safety, and low cost. • However, the emergence of enteric pathogens resistant to these agents is limiting their usefulness.

Drug Therapy Contd….. • 4. Antimicrobials • Cotrimoxazole: MOA:P-aminobenzoic acid (PABA) by dihydropteroatesynthaseenzyme is converted to Dihydrofolic acid (DHFA), which is converted to Tetrahydrofolic acid (THFA) by dihydrofolatereductaseenzyme. THFApurines DNA. • SMX  compete with PABA and 1st enzyme • TMP  compete with 2nd enzyme • Net result synergism between TMP-SMX to inhibit DNA synthesis. • ADR: hematological disturbance, crystaluria, allergy, GI upset, drug interaction (SMX displace some drugs), hepatic injury & induce folate deficiencymegaloblastic anemia "mainly in pregnancy" • Alternatives: • Fluoroquinolones e.g. ciprofloxacin# DNA gyrase and so DNA synthesis • Third-generation cephalosporins e.g. ceftriaxone, cefotaxime# cell wall synthesis. • Although FQs are not approved for use in children because lesions on cartilage are reported in juvenile animals, clinical trials using FQs in children are performed because of the emergence of multidrug-resistant enteropathogens in some areas, and no problems have been reported related to these antibiotics. • Azithromycinmacrolide# protein synthesis. • Metronidazole(drug of choice For diarrhea due to E. histolytica • MOA • Dose: 500 mg TDS 7-10 days • Other uses: 1. Anaerobic infection 2. PU (for H. Pylori) • 2. Trichomonas 4. Giardia • Common ADR:bitter taste, dark urine and GIT dyspepsia

The only medications used in the treatment of giardiasis are antimicrobial agents to eradicate the organism in the bowel. Many drugs useful in amebiasis are also effective in giardiasis. • Metronidazole: 200mg tds (15 mg/kg/day) X 7d or 2g qd x3d • Tinidazole: 600 mg qdX7d or 2g single dose • Secnidazole: 2g single dose • Mepacrine: 100mg tds X 5d more side effects • Quiniodochlor: 250 mg tds X 7 d or Iodoquinol as an alternative • Furazolidone: 100mg tds X 7d • Partly absorbed from intestine, Excreted in urine which turns orange • Side effects: mild and infrequent, Nausea, headache and dizziness

Classification of antihelmintic drugs Classification according to the type of helminthes Antihelmintic Drugs ↓

Antihelminthic drugs for common parasites

Anthelmintics Pyrantelpamoate • Kinetics: Given orally, poorly absorbed, and mainly excreted in feces. • MOA: It is a depolarizing NM blocker  release of AChand inhibition of CHE enzyme stimulation of ganglionicreceptorsworm paralysis & expulsion outside. • Uses: -The standard dose is 11 mg/kg (maximum 1g) • Ascariasis, Ancylostoma single dose & may be repeated in heavy infestation after 2 wks (treat anemia in case of ancylostoma) • Enterobius single dose & repeated in 2- 4 weeks. • ADR: Mild, GIT upset, neurological and allergy. • Cautions: Better avoided in patients with liver dysfunction and pregnancy. Mebendazole • Kinetics: < 10% of the oral dose is absorbed, metabolized in the liver and excreted in urine • MOA:blocks movement of secretory granules & other subcellular organelles in the parasitedisappearance of cytoplasmic microtubules irreversibly impairing glucose uptake  immobilizes the parasite slowly dies. • Uses: The tablets should be chewed before swallowing. • a. Ascaris, Ancylostoma, T. trichiura: 100 mg X 2 X 3 and can be repeated after 2 Wks • b. Enterobius: 100 mg once and repeated at 2 and 4 weeks. Family TTT • c. Hydatid disease: 50 mg/kg in 3 divided doses daily for 3 months. • ADR: -Low doses no ADR or mild GIT upset & hypersensitivity • -High dosespruritus, rash, eosinophilia, neutropenia, musculoskeletal pain, fever and rarely alopecia, glomerulonephritis, cough, gastritis, abnormal liver functions and agranulocytosis. • Contraindications:-Better avoided in severe liver disease, pregnancy & <1 year of age.

Anthelmintics Albendazole • Kinetics: Erratically absorbed, first-pass metabolism in the liver, excreted mainly in urine and to a lesser extent in the feces. It is taken on an empty stomach for intra-luminal parasites. • MOA: blocks glucose uptake by larva and adult parasites depleting glycogen storesdecreasing formation ofATPparasite paralysis and death. • Uses: • Enterobius: a single dose of 400 mg orally to be repeated after 2 Wks • Ascariasis, Ancylostoma: 400 mg/d for 2- 3 days. • Strongyloldiasis: 400 mg twice daily for 7- 14 days • ADR: Mild, more prominent with long courses. • -Epigastric pain, N, V, D, headache, dizziness, lassitude, insomnia, reversible aminotransferase elevations. Rarely jaundice, leucopenia • Contraindications: Children < 2 years, pregnancy, with liver cirrhosis Ivermectin • Kinetics: given orally, has a wide tissue distribution and is eliminated with its metabolites in feces. • MOA: Intensifying GABA-mediated transmission of signals in peripheral nerves of the parasite  paralysis death. • Uses: For strongyloidiasis, single dose of 200 mg/kg cure rate > 80%. The dose may be repeated. Double the dose is used in bancroftianfilariasis • ADR: -Mazotti reaction in 5-30% of patients: In onchocerciasis TTT, due to killing of microfilariae. It includes fever, headache, dizziness, weakness, rash, pruritus, diarrhea, joint & muscle pains, hypotension, tachycardia, lymphadenitis & peripheral edema. It is controlled by aspirin and anti-histamines and may be steroids. • - Corneal opacity & other eye lesions: usually mild & resolve without TTT • Contraindications: • -Not used with barbiturates, benzodiazepines and valproic acid. • -Not used in pregnancy or in children under 5 years and lactating mothers or in patients with impairment blood-brain barrier

Anthelmintics BithionolMOA unknown • Kinetics: PO daily dose of 50 mg/kg in three divided doses after meals on alternate days for 10- 15 doses and excretion is via the kidney. • Adverse reactions:N, V, D, abdominal cramps, dizziness and headache may occur. Less frequent are allergic reactions. • Contraindications: -used with caution in children < 8 y • Stop treatment if there is toxic hepatitis or leucopenia. Praziauantel • Kinetics:rapidly absorbed, 80% plasma bound, rapidly metabolized to inactive products and excreted via kidneys. • MOA: ↑cell membrane permeability to Ca massive Ca influx marked tetanic contraction of the worm, followed by muscle paralysis, associated with disintegration of the tegmendeath of the parasite. • Uses:40 mg/kg once for S. haematobium & 40 mg/kg in two divided doses for S. mansoni. • -Cure rates are 75- 95%. • ADR:-It is very bitter  may induce vomiting, Mild and transient C.N.S., G.I.T. upset, allergy & Elevation of liver enzymes • -Reactions are severe with increase the dose. • Contraindications & cautions: • Ocular cysticercosis as parasite destruction in the eye may cause irreparable damage. • Reduce the dose in liver impairment. • Avoid alertness-required activities during treatment with the drug. • Not recommended in children < 4Y, during pregnancy and avoid breast feeding on the day of treatment and for 3 subsequent days.

Anthelmintics • Niclosamide • MOA:Niclosamide may act by uncoupling oxidative phosphorylation or by acti-vatingATPases death of the scoleces and segments of cestodes digestion of the parasite • Clinical use: • It is one of two drugs of choice (with praziquantel) for infections caused by beef, pork, and fish tapeworm infections. Scoleces and cestode segments are killed, but ova are not. • Effective in the treatment of infections due to small and large intestinal flukes. • Toxicity: Toxic effects are usually mild but include • GI distress, • headache, • rash, and fever • (Some of these effects may result from systemic absorption of antigens from disintegrating parasites)

Common parasitic Infections of GIT ( Infectious diarrhea)