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The drugs recommended by WHO for soil-transmitted helminthiasis are albendazole, mebenda-zole, levamisole, pyrantel and ivermectin; and for schistosomiasis they are praziquantel and oxam-niquine for S. mansoni (Table 11.3).2


The benzimidazoles, albendazole and mebenda-zole, have broad-spectrum activity against round-worm, whipworm, hookworm, pinworm and wire-worm species. The action of albendazole on the parasite is to bind to tubulin, inhibit microtubule assembly, decrease glucose absorption and inhibit

Table 11.3 Drugs for the treatment of soil-transmitted helminthisasis and schistosomiasis (from reference 2)

Drug and formulation


(tablets 200 and 400mg, suspension 100mg/5ml)

Therapeutic activity ascariasis +++ trichuriasis ++ hookworm infection +++ strongyloidiasis ++

Pediatric dosage

400mg stat dose (200mg if <10 kg) (daily for 3 days)

Ivermectin (tablets 6mg)

ascariasis +++ trichuriasis + strongyloidiasis ++

200|jg/kg stat dose


(tablet 40 mg, syrup 40 mg/5 ml)

ascariasis +++ trichuriasis + hookworm infection ++

2.5 mg/kg stat dose (repeat after 7 days)


(tablets 100mg and 500 mg suspension 100mg/5ml)

ascariasis +++ trichuriasis ++ hookworm infection ++

500mg stat dose

100 mg twice a day for 3 days

(or 500mg stat dose)

Pyrantel (tablets 250mg, suspension 50mg/5ml)

ascariasis +++ hookworm infection ++

10 mg/kg stat dose (repeat daily for 4 days)

Praziquantel (tablet 600mg)

schistosomiasis +++ (all species)

40-60 mg/kg stat dose or in divided doses


(capsules 250mg, syrup 250mg/ml)

schistosomiasis +++ (S. mansoni only)

20 mg/kg stat dose

(or 20-60mg/kg divided doses)

fumarate reductase. It is poorly soluble in water, but well absorbed with a fatty meal. It is rapidly metabolized in the liver to the active form, alben-dazole sulfoxide, which has a serum half-life of 8-9 h, and is excreted by the kidneys. It is usually very well tolerated as a single dose or daily for 3 days, with gastrointestinal symptoms (e.g. pain, diarrhea, nausea or vomiting) in only 1.3% of courses.156 Worm migration is uncommon with albendazole treatment, but prolonged therapy may cause alopecia, reversible marrow suppression or hepatocellular damage. Albendazole should be avoided in pregnancy and in children under 6 months of age.

Albendazole 400mg (200mg if < 10kg) as a single dose or mebendazole 200mg (100mg if <10kg) daily for 3 days are the treatments of choice for ascariasis, but pyrantel pamoate, piperazine tartrate and levamisole are equally effective and may be cheaper in the context of the developing world. The benzimidazoles and pyrantel have potential teratogenicity so should be used with caution in infancy. The first-line treatment for hookworm is albendazole 400mg as a single dose (200mg if < 10kg) or mebendazole 100mg twice daily for 3 days (or single dose of 500mg if over 2 years of age). Alternatives are pyrantel pamoate or levamisole, but ivermectin is ineffective and bephenium is no longer recommended.

For clinically significant Trichuris infections, the treatment of choice is albendazole 400 mg (or mebendazole 200mg) daily for 3 days. Half of these doses are used for children < 10kg, but clinical judgment must be used to assess risk-benefit in this age group. Single doses are used for mass campaigns or 3-6 months of prophylaxis, but iver-mectin, pyrantel, levamisole and piperazine are mostly ineffective against Trichuris. Treatment of heavy infections associated with malnutrition should result in catch-up growth. A community-based Mexican trial of 622 children with asymptomatic trichuriasis followed their growth for 12 months after treatment with albendazole 400 mg daily for 1 or 3 days, or pyrantel 11 mg/kg as a single dose.157 Although children with heavy pretreatment worm loads had improved catch-up growth on 3 days of albendazole compared to pyrantel, those with low infection had worse growth parameters, so the authors suggest that 3-day albendazole may have 'toxic effects' on growth. This resulted in discouragement of its routine use in children under 2 years, but such an effect has not been confirmed in Tanzania, so there has been a recent call for reinstitution of anti-helminthic treatment in children under 24 months.158

A recent adult study of albendazole (800 mg twice daily for 14 days) in HIV-related persistent diarrhea showed 46% clearance rates of protozoa at 3 weeks and 39% clinical resolution and mucosal recovery at 6 weeks.159 A review of albendazole studies in adults and children calculated overall cure rates after standard treatment (single 400 mg dose, except for S. stercoralis, H. nana and Taenia requiring 3 days) of 98% for pinworm, 95% for Ascaris, 85% for Taenia species, 78% for hookworm, 68% for H. nana, 62% for Strongyloides and 48% for Trichuris.156 Egg reduction rates after albendazole treatment were also high for Ascaris (99%), hookworm (88%) and Trichuris (75%). The cure rates for hookworm in children differed by species with rates of 91% for A. duodenale but only 67% for N. americanus.156 Heavy Trichuris infections require at least 3 days of albendazole for high cure rates in children, but a Filipino study found that a combination of single-dose albenda-zole plus ivermectin gave high cure rates for single-dose therapy.160 Albendazole 400 mg daily for 5 days is an alternative treatment for giardia-sis.161 Albendazole 400mg daily for 3 days and repeated a week later is also highly effective in acute strongyloidiasis in children, but parasitolog-ical cure rates are only 45-75% so all larvae may not be eradicated.

A Turkish study randomized 162 school children with halitosis to mebendazole vs. placebo and documented a significant improvement in their chronic bad breath in the treatment group for those with intestinal parasites (pinworm, round-worm, giardiasis, Taenia or whipworm).162


Pyrantel is a depolarizing neuromuscular blocking agent which paralyses worms until they are expelled in feces. Pyrantel pamoate is active against Ascaris and Enterobius, only partially effective against hookworm and ineffective against Trichuris and Strongyloides. It is given as a single dose of 20mg/kg up to 750mg orally (repeat after 7 days if heavy infection) or 10 mg/kg daily for 3 days for hookworm.


Levamisole is an immune stimulant which is effective against Ascaris and hookworm, and may be more effective for intestinal obstruction from roundworms, since it acts by paralyzing the myoneural junction of the worm. The dosage is 3mg/kg as a single dose.


Ivermectin has broad-spectrum activity against helminths and filariasis, but is the drug of choice against strongyloidiasis. Ivermectin is well absorbed orally, accumulating in adipose tissue, metabolized in the liver, highly protein bound with a serum half-life of 12 h and excreted in stool. It is generally well tolerated, with occasional abdominal distension, chest tightness or wheezing. In a Tanzanian study of children, ivermectin was found to be more effective than albendazole for curing Strongyloides, equally effective for Ascaris, less effective for Trichuris and ineffective against hookworm infections.163 Another African study of ivermectin in intestinal nematode infections found little effect on either prevalence or intensity of N. americanus hookworm or Trichuris, and only a modest effect on Ascaris.164

Ivermectin 200|g/kg as a single dose has a reported cure rate of 83% for Strongyloides. In complicated or disseminated infection, ivermectin should be repeated on days 2, 15 and 16 to decrease relapse. In immunosuppressed patients, treatment is not always successful, and may need to be repeated at monthly intervals, or a longer course given. An adult open-label study of 60 patients with strongyloidiasis compared singledose ivermectin with albendazole for 3 days and found higher cure rates with the former (83% vs. 38%).165 Another adult study comparing iver-mectin with thiabendazole documented high cure rates for both drugs but the adverse effects were much greater for thiabendazole (e.g. disorientation, fatigue, nausea and anorexia).166 A comparative trial in 301 children from Zanzibar with S. stercoralis larvae in stool had cure rates of 82.9% with single-dose ivermectin compared to only 45.0% with 3 days of albendazole.163 Disseminated disease has a high mortality, so may require iver-mectin over 3-4 weeks.


Metronidazole is used for giardiasis and amebiasis. It is activated by reduction of its 5-nitro group, is concentrated in anaerobic organisms and interacts with DNA to cause microbial death. It is not well tolerated, with anorexia and gastrointestinal upset occurring after several days' treatment.167 The dose of metronidazole has been controversial, but a computer simulation study using the conventional 30 mg/kg per day regime calculated that steady state was reached at 24 mg/kg per day in rehabilitated children and at 12 mg/kg per day in severely malnourished children using the twice daily dosage.168 Patients with immunodeficiency may require treatment for 6-8 weeks for giardiasis. The American Academy of Pediatrics and Centers for Disease Control recommend that asymptomatic Giardia infections not be treated.169,170 Asymptomatic cyst excretors, even at day-care centers, do not warrant treatment.170,171

Amebic colitis or dysentery should be treated with metronidazole plus a luminal agent such as dilox-anide furoate, paromomycin or iodoquinol. Although improvement usually occurs within 3-4 days of treatment, metronidazole should be continued for a minimum of 10 days to eliminate intestinal colonization with risk of relapse. Treatment of asymptomatic cyst passers is inappropriate for E. dispar, but is warranted for E. histolytica in developed countries but probably not practical in most of the developing world where the disease in endemic. The dosage for treatment of acute amebic colitis is metronidazole 35-50mg/kg per day in three divided doses for 10 days. The intraluminal agents are used for eradicating cyst passage. The dosages are: iodoquinol 30-40mg/kg per day in three divided oral doses for 20 days, or diloxanide furoate 20mg/kg per day in three divided doses, or paromomycin 25-35mg/kg per day in three divided doses for 7 days.


Tinidazole is another 5-nitroimidazole with a similar mechanism of action to that of metronida-zole but a convenient single dosage. A Cochrane review of 34 trials on drugs for treating giardiasis concluded that tinidazole 50mg/kg in a single dose had a higher clinical cure rate than a short course of treatment with metronidazole, albendazole or secnidazole.172


Nitazoxanide is a new broad-spectrum antimicrobial agent with activity against nematodes, trematodes, anaerobic bacteria and protozoal parasites such as Cryptosporidium. It is metabolized in blood to tizoxanide, which inhibits the key enzyme pyruvate ferredoxin oxidoreductase of target organisms, and is excreted in urine and feces. Adverse effects tend to affect the gastrointestinal tract, but appear to be mild and tran-sient.173 A 3-day course of 100-200mg 12-hourly in children (adults 500mg) is effective against giardiasis, amebiasis, Blastocystis hominis, Balantidium coli, Isospora belli, Ascaris, Trichuris, hookworm and Hymenolepis nana.168 In view of this wide spectrum of action, single-dose therapy in combination with other drugs is under investigation for community treatment programs.

Two Egyptian randomized placebo-controlled trials of diarrheal subjects have shown that nita-zoxanide was associated with resolution of the diarrhea within 7 days in about 80% of cases of giardiasis, amebiasis or cryptosporidiosis compared to about 40% in the placebo group.174,175 A Mexican study of 275 children with helminth or protozoan infections documented a higher (but non-significant) parasite eradication rate with 3 days of nitazoxanide (79%) than with 3 days of mebendazole plus quifamide (74%).176 Another Mexican study has documented its in vitro effectiveness against trophozoites of E. histolytica and Giardia.177 Nitazoxanide was best for eradication of H. nana (90-100%) and worst for giardiasis (56-74%). Comparative studies of Peruvian children with ascariasis, trichuriasis, hymenolepiasis and giardiasis reported cure rates for nitazoxanide of 89%, 89%, 82% and 85%, respectively, compared with 91%, 58%, 96% and 75-80% for albendazole, praziquantel (H. nana) or metronidazole (Giardia), respectively.178,179 A recent Zambian trial of 3 days of nitazoxanide (vs. placebo) in 100 children with cryptosporidiosis showed clinical response rates of 56 vs. 23% and parasitological response rates of 52 vs. 14% in HIV-seronegative children, but no significant response in HIVseropositive cases.180


Paromomycin is a poorly absorbed aminoglycoside which reaches high concentrations in the intestine, but absorbed drug is excreted renally and is potentially ototoxic and nephrotoxic. It has been used for cryptosporidial diarrhea in AIDS patients, requiring continuous maintenance therapy, but appears now to be ineffective.181,182

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  • albertina
    What are the first line drugs treatment of hookworm?
    8 years ago

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