A. Overview of Agents [1]

1. Benzimidazoles [21]
   1. Bind free ß-tubulin, inhibit tubulin polymerization
   2. Albendazole (Albenza®) - most commonly used in USA
   3. Thiabendazole (Mintezol®)
   4. Mebendazole (Vermox®) - safe in second and third trimesters of pregnancy [3]
2. Ivermectin (Stromectol®)- semisynthetic macrocyclic lactone
3. Praziquantel
4. Fumagillin
5. Paromomycin
6. Trimethoprim-Sulfamethoxazole (TMP-SMX, Bacrim®, Septra®)
7. Metronidazole (Flagyl®) - active against giardia, amoeba
8. Atovaquone
9. Antimalarials: chloroquine, mefloquine, primaquin
10. Miscellaneous Agents (see below)
11. Centers for Disease Control contact number 404-639-3670, 404-639-2888

B. Albendazole (Albenza®)

1. Binds free ß-tubulin, preventing polymerization
2. No resistance to date in humans
3. Antihelminthic Activities [21]
   1. Echinococcus - 10mg/kg divided, usually 400mg po bid, may be given indefinitely [19]
   2. Cysticercosis
   3. Ascariasis
   4. Trichuriasis
   5. Enterobiasis
   6. Hookworm - single dose superior to mebendzole and pyrantel
   7. Strongyloidiasis
4. Antiprotozoal Activities
   1. Giardiasis
   2. Microsporidiosis (AIDS) - 400mg po bid is usually first line
5. Albendazole should be combined with cyst drainage in hepatic echinococcus [4]
6. About 45% reduction in seizures with neurocysticercosis and seizures with albendazole + dexamethasone for 10 days [20]
7. Presumptive administration to all immigrants at risk for parasitosis is cost-effective [5]

C. Ivermectin (Stromectol®) [6]

1. Appears to open chloride (or glutamate) sensitive channels
2. May be due to interruption of GABA-induced neurotransmission
3. Active against many Nematodes
   1. Onchocerciasis (river blindness)
   2. Lymphatic filariasis (lymphatic obstruction, usually due to Wuchereria bancrofti)
   3. Common roundworms: ascaris, trichuris, enterobius
4. Active against ectoparasites: scabies; head lice (200µg/kg x 1 dose) [7,8]
5. Combination with albendazole most effective against blood-borne filariasis [9]
6. Single annual diethylcarbamazine ± ivermectin can reduce serious human filariasis infections by 50-85% and reduce mosquito carriage by up to 98% [10,17]

D. Praziquantel (Biltricide®)

1. Poorly understood mechanism of action
   1. Interferes with calcium metabolism
   2. Causes flaccid paralysis of flukes
   3. Immune response by host is required for praziquantel efficacy
2. Drug of choice for all forms of schistosomiasis
   1. S. haematobium and S. mansoni - 20mg/kg in bid x 1 day
   2. S. japonicum and S. mekongi - 20mg/kg tid x 1 day
3. Active against liver, lung, intestinal and nervous system flukes
4. Active against Tapeworms
   1. Dwarf tapeworms (Hymenolepis nana) - 25mg/kg x 1 dose
   2. Animal tapeworms (fish, cow, pig, dog) - 5-10mg/kg x 1 dose
5. Antiseizure medications increases praziquantel metablism, lower levels
6. Oxamniquine may be used for some resistant Schistosoma mansoni (15mg/kg x 1 dose)

E. Atovaquone (Mepron®) [11]

1. Mechanism
   1. Inhibits parasite mitochondrial respiratory chain
   2. Atovaquone blocks subsequent de novo pyrimidine synthesis
2. Effective against malaria, toxoplasmososis, and pneumocystis
3. Combination with proguanil (Malarone®)
   1. Comnbination required against malaria to prevent rapid resistance
   2. Effective for prevention and cure of all malaria species
   3. Combination also highly effective against chloroquine resistant P. falciparum malaria

F. Nitazoxanide (Alinia®) [15,18]

1. Nitrothiazolyl-salicylamide derivative
2. Likely inhibits pyruvate:ferredoxin oxidoreductase (PFOR) electron transfer reactions
3. Broad spectrum activity against protozoa, nematodes, cestodes, trematodes, bacteria
   1. Cryptosporidiosis (C. parvum), particularly in HIV negative patients
   2. Giardia lamblia
   3. Isospora belli
   4. Entameba histolytica
   5. Helminths: Ascaris, Ancylostoma, Trichuris, Taenia, Hymenolepis, Fasciola
   6. Balantidium coli
   7. Strongyloides stercoralis
4. Three day course 100-200mg po bid cures ~50% of HIV negative patients with C. parvum
5. Available as 100mg/5mL suspension (pills in development)
   1. Dose (Giardiasis, HIV-) age 12-47 months: 100mg q12 hours x 3 days
   2. Dose (Giardiasis, HIV-) age 4-11 years: 200mg q 12 hours x 3 days
6. Additional therapy cures ~90% of initial non-responders (HIV negative only)
7. Very well tolerated; some abdominal pain, diarrhea, vomiting but similar to placebo rates

G. Other Agents [1]

1. Fumagillin
   1. Produced by Aspergillus fumigatus
   2. Used for ocular microsporidiosis (keratoconjunctivitis) in HIV infection
   3. Suppresses proliferation specifically of this organism
   4. Effective for systemic and gastrointestinal chronic microsporidiosis infections [12]
   5. Side effects include thrombocytopenia and neutropenia in some patients
2. Paromomycin (Humatin®) [18]
   1. Nonabsorbed antiparastitic useful for luminal gastrointestinal infections
   2. Secondary therapy for amoebic infection
   3. Primary therapy for mild giardiasis in pregnant women
   4. For cryptosporidiosis in HIV infection 500mg po tid-qid reduces infection
   5. Lifelong suppressive therapy with 500mg po bid is required to prevent relapse
   6. Dose for children (C. parvum infection): 25-35mg/kg/d in 3 doses x 7 days
3. TMP-SMX (Bactrim®, Septra®)
   1. Effective against Cyclospora related diarrhea [13]
   2. Also effective against Isospora (particularly in HIV) in high doses
   3. Pyrimethamine alone 75mg po qd also effective against Isospora
4. Nifurtimox (Lampit®)
   1. T. cruzi (Chagas' Disease, American Trypanosomiasis) treatment of choice
   2. Dose is 8-10mg/kg/d in 3-4 doses and 3-4 months
   3. Anorexia, vomiting, weight loss, memory problems, sleep disorders, paresthesias
   4. Rare: seizures, fever, pulmonary abnormalities
5. Proguanil [11]
   1. Dihydrofolate reductase antagonist
   2. Effective and very well tolerated against malaria
   3. Combinations with atovaquone are most effective, including chloroquine resistant bugs
6. Malathion [7,14]
   1. Used for treatment of Head Lice - Pediculus humanus variant corporis
   2. These are blood-sucking ectoparasites
   3. Malathione is an organophosphate compound based on pesticides
   4. Irreversible cholinesterase inhibitor
   5. Now available in USA, as 0.5% shampoo in isopropanol
   6. Leave on hair x 12 hours, then wash off
   7. Typically effective after one treatment
   8. Two treatments more effective than mechanical removal of lice [14]
7. Miltefosine [16]
   1. Hexadecylphosphocholine - phosphocholine analog
   2. Good efficacy in vitro against Leishmania
   3. Oral miltefosine 50-100mg/day x 28 days is effective in visceral leishmaniasis
   4. Generally well tolerated with vomiting (38%) and diarrhea (20%)
8. Diethylcarbamazine (Hetrazan®) - visceral larva migrans
9. Suramin
   1. Treatment of choice for African tripanosomiasis, sleeping sickness
   2. Includes T. brucei gambiense, T. brucei rhodesiense
   3. Dose is 100-200mg IV (test dose) then 1gm IV on days 1,3,7,14,21
   4. Frequent vomiting, pruritis, urticaria, paresthesias, peripheral neuropathy
   5. Shock, kidney damage, optic atrophy may also occur

References

1. Antiparasitic Agents. 1998. Med Let. 40(1017):1
2. Liu LX and Weller PF. 1996. NEJM. 334(18):1179
3. de Silva NR, Sirisena JLGJ, Gunasekera DPS, et al. 1999. Lancet. 353(9159):1145
4. Khuroo MS, Wani NA, Javid G, et al. 1997. NEJM. 337(13):881
5. Muennig P, Pallin D, Sell RL, Chan MS. 1999. NEJM. 340(10):773
6. Burnham G. 1998. Lancet. 351(9112):1341
7. Malathione for Head Lice. 1999. Med Let. 41(1059):73
8. Chosidow O. 2000. Lancet. 355(9206):819
9. Addiss DG, Beach MJ, Streit TG, et al. 1997. Lancet. 350:480
10. Bockarie MJ, Alexander NDE, Hyun P, et al. 1998. Lancet. 351(9097):162
11. Lell B, Luckner D, Ndjave, et al. 1998. Lancet. 351(9104):709
12. Molina JM, Tourneur M, Sarfati C, et al. 2002. NEJM. 346(25):1963
13. Herwaldt BL, Ackers ML, Cyclospora Working Group. 1997. NEJM. 336(22):1548
14. Roberts RJ, Casey D, Morgan DA, Petrovic M. 2000. Lancet. 356(9229):540
15. Amadi B, Mwiya M, Musuku J, et al. 2002. Lancet. 360(9343):1375
16. Sundar S, Jha TK, Thakur CP, et al. 2002. NEJM. 347(22)1739
17. Bockarie MJ, Tisch DJ, Kastens W, et al. 2002. NEJM. 347(23):1841
18. Nitazoxanide. 2003. Med Let. 45(1154):29
19. McManus DP, Zhang W, Li J, Bartley PB. 2003. Lancet. 362(9392):1295
20. Garcia HH, Pretell EJ, Gilman RH, et al. 2004. NEJM. 350(3):249
21. Keiser J and Utzinger J. 2008. JAMA. 299(16):1937