Abstract
Drug development offers potential solutions to a number of tropical health diseases, although the expense of pharmaceutical research and lack of return on investment has limited the production of new agents. The greatest successes have been through the development of single dose therapy and mass treatment control programmes for a number of diseases. We review some of the current treatment regimens for malaria, intestinal helminth infection, onchocerciasis, filariasis and schistosomiasis, and their use in clinical practice.
Geographical spread and emergence of drug resistant parasites have hindered the control of malaria, the most important global parasitic infection. Artemisinin compounds have proved effective antimalarial agents producing rapid reduction of parasite load and can be used in combination treatment regimens to combat multidrug resistance.
Intestinal helminth infections are widespread, giving rise to nutritional deficiencies and impaired childhood cognitive development. Pregnant women in developing countries are at increased risk of morbidity. Treatment with a single dose benzimidazole such as albendazole or mebendazole has beneficial effects on morbidity and rates of transmission.
Diethylcarbamazine has been used in the treatment of onchocerciasis and human filariasis. A complicated escalating dose regimen over several weeks is associated with systemic and allergic reactions and may require corticosteroid cover. Simplified regimens for mass population treatment with ivermectin have proved useful and been used in combination with single dose albendazole and diethylcarbamazine. The African Programme for Onchocerciasis Control in West and Central Africa has been one of the most successful mass control programmes virtually eliminating new infections by a combination of chemotherapy, education and vector control.
Schistosomiasis is of increasing importance as a result of the creation of new snail habitats by agricultural and economic development. Praziquantel has become the most widely available and effective chemotherapy for schistosomiasis. There have been a number of reports of persistent schistosome egg shedding after treatment posing concerns about the emergence of drug resistance.
Eflornithine has been successfully used in patients with human trypanosomiasis failing melarsoprol therapy however expense and availability have limited its potential.
Mass control treatment programmes have targeted schoolchildren, adolescents and pregnant women. The integration of schistosomiasis, onchocerciasis, filariasis and helminth control programmes has been considered as a cost-effective method of delivering treatment. It is likely that future control will be based on this optimisation and integration of existing regimens, rather than the development of new agents.
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References
World Health Organization (WHO). Fake drugs: a scourge on the system. WHO Drug Info 1995; 9: 127–9
Pecoul B, Varaine F, Keita M, et al. Long acting chloramphenicol versus intravenous ampicillin for treatment of bacterial meningitis. Lancet 1991; 338: 862–3
Doua F, Boa FY, Schechter PJ et al. Treatment of human gambiense trypanosomiasis with difluoromethylornithine (eflornithine). Am J Trop Med Hyg 1987; 37: 525–33
Pecoul B, Chirac P, Trouiller P, et al. Access to essential drugs in poor countries: a lost battle? JAMA 1999; 281: 361–6
Baird JK. Resurgent malaria at the Millennium: control strategies. Drugs 2000; 59(4): 719–43
Martens P Hall L. Malaria on the move: human population movement and transmission. Emerg Infect Dis 2000; 6: 103–9
White NJ. Not much progress in the treatment of cerebral malaria. Lancet 1998; 352: 594–5
Murphy GS, Basri H, Purmomo K, et al. Vivax malaria resistant to treatment and prophylaxis with chloroquine. Lancet 1993; 341: 96–100
Watt G, Loesuttivibool L, Shanks GD, et al. Quinine with tetracycline for the treatment of drug resistant falciparum malaria in Thailand. Am J Trop Med Hyg 1992; 47: 108–11
Phillips-Howard PA, ter Kuile FO. CNS adverse effects associated with antimalarials: fact or fiction? Drug Saf 1995; 12: 370–83
ter Kuile FO, Nosten F, Thieren M, et al. High dose mefloquine in the treatment of multidrug resistant falciparum malaria. J Infect Dis 1992; 166: 1393–400
Looareesuwan S, Viravan C, Vanijanonta S, et al. Randomised trial of artesunate and mefloquine alone and in sequence for acute uncomplicated falciparum malaria. Lancet 1992; 339: 821–4
Nosten F, Luxemburger C, ter Kuile FO, et al. Treatment of multidrug resistant Plasmodium falciparum malaria with three day artesunate-mefloquine combination. J Infect Dis 1994; 170: 971–7
Nosten F, ter Kuile FO, Luxemburgher C. Cardiac effects of antimalarial treatment with halofantrine. Lancet 1993; 341: 1054–6
de Alencar FE, Cerutti C, Durlacher RR, et al. Atovaquone and proguanil for the treatment of malaria in Brazil. J Infect Dis 1997 Jun; 175(6): 1544–7
Hien TT, White NJ. Qinghaosu. Lancet 1993; 341: 603–8
Udomsangpetch R, Pipitaporn B, Krishna S, et al. Antimalarial drugs reduce cytoadherence and rosetting of Plasmodium falciparum malaria. J Infect Dis 1996; 173: 691–8
Boele van Hensbroek M, Onyiorah E, Jaffar S, et al. A trial of artemether or quinine in Vietnamese adults with severe falciparum malaria. N Engl J Med 1996 Jul; 335: 69–75
Hien TT, Day NPJ, Phu NH, et al. A controlled trial of artemether or quinine in Vietnamese adults with severe falciparum malaria. N Engl J Med 1996 Jul; 335: 76–83
Brewer TG, Peggins JO, Grate SJ, et al. Neurotoxicity in animals due to arteether and artemether. Trans R Soc Trop Med Hyg 1994; 88 Suppl. 1: S33–6
Miller LG, Panosian CB. Ataxia and slurred speech after Artesunate treatment for falciparum malaria [letter]. N Engl J Med 1997 May; 336: 1328
White NJ. Drug resistance in malaria. Br Med Bull 1998; 54(3): 703–15
White NJ. Current concepts: the treatment of malaria. N Engl J Med 1996 Sept; 335: 800–6
Crompton DWT. How much human helminthiasis is there in the world? J Parasitai 1999; 85(3); 397–403
Callender JEM, McGregor SM, Walker S, et al. Trichuris infection and mental development in children [letter]. Lancet 1992; 339: 180
Nokes C, Bundy DAP. Does helminth infection affect mental processing and educational achievement. Parasitai Today 1994; 10: 14–8
Anderson RM, May RM. Infectious disease of humans: dynamics and control. New York (NY): Oxford University Press, 1991: 433–606
Stephenson L, Latham M, Adams E, et al. Weight gain of Kenyan children infected with hookworm, Trichuris trichiura and Ascaris lumbricoides is improved following once- or twice-yearly treatment with albendazole. J Nutr 1993; 123: 656–65
Stephenson L, Latham M, Adams E, et al. Physical fitness, growth and appetite of Kenyan schoolboys with hookworm, Trichuris trichiura and Ascaris lumbricoides infections are improved four months after a single dose of albendazole. J Nutr 1993: 123: 1036–4
Dickson R, Awasthi S, Williamson P, et al. Effects of treatment for intestinal helminth infection on growth and cognitive performance in children: systematic review of randomised trials. BMJ 2000; 320: 1697–701
Anonymous. Mass therapy is cost effective for controlling intestinal nematodes. Drug Ther Perspect 1995 Nov; 6 (10): 14–16
De Silva N, Guyatt H, Bundy D. Antihelmintics: a comparative review of their clinical pharmacology. Drugs 1997 May; 53(5): 769–88
World Health Organization (WHO). WHO model prescribing information: drugs used in parasitic diseases. 2nd ed. Geneva: WHO, 1995
De Silva NR, Sirisena JL, Gunasekera DP, et al. Effect of mebendazole therapy during pregnancy on birth outcome. Lancet 1999 Apr; 353: 1145–9
Bekhti A, Pirotte J. Cimetidine increases the serum mebendazole concentrations: implications for treatment of hepatic hydatid cysts. Br J Clin Pharmacol 1987; 24: 390–2
Wen H, Zhang HW, Muhmut M, et al. Initial observation on albendazole in combination with cimetidine for the treatment of human cystic echinococcosis. Ann Trop Med Parasitai 1994; 88(1): 49–52
Olds GR, King C, Hewlett J, et al. Double-blind placebo controlled study of concurrent administration of albendazole and praziquantel in schoolchildren with schistosomiasis and geohelminths. J Infect Dis 1999 Apr; 179(4): 996–1003
World Health Organization. Onchocerciasis control programme in West Africa [online]. Available from: URL: http://www.who.int/ocp/ [Accessed 2000 Sep 6]
Brownlee DJA, Holden-Dye L, Walker RJ. Actions of the anti-helmintic ivermectin on the pharyngeal muscle of the parasitic nematode, Ascaris suum. Parasitology 1997; 115: 553–61
Greene BM, Taylor HR, Cupp EW, et al. Comparison of ivermectin and Diethylcarbamazine in the treatment of onchocerciasis. N Engl J Med 1985 Jul; 313(3): 133–41
Lariviere M, Aziz M, Weimann D, et al. Double-blind study of ivermectin and diethylcarbamazine in African onchocercasis patients with ocular involvement. Lancet 1985 Jul; II: 174–7
Burnham G. Ivermectin treatment of onchocercal skin lesions: observations from placebo-controlled double-blind trial in Malawi. Am J Trop Med Hyg 1995; 52: 270–6
Awadzi K, Dadzie KY, Klager S, et al. The chemotherapy of onchocercasis: studies with ivermectin in onchocerciasis patient in northern Ghana, a region with long acting vector control. Trop Med Parasitai 1989; 40: 361–6
Burnham G. Adverse effects to ivermectin treatment for onchocerciasis: results of a placebo-controlled double-blind trial in Malawi. Trans R Soc Trop Med Hyg 1993; 87: 313–7
Guderian RH, Anselmi M, Espinel M, et al. Successful control of onchocerciasis with community based ivermectin distribution in the Rio Santiago focus in Ecuador. Trop Med Int Health 1997 Oct; 2(10): 982–8
Marti H, Haji HJ, Savioli L, et al. A comparative trial of a single-dose ivermectin versus three days of albendazole for treatment of Strongyloides stercoralis and other soil transmitted helminths in children. Am J Trop Med Hyg 1996; 55: 477–81
Noroes J, Dreyer G, Santos A. Assessment of efficacy of diethylcarbamazine on adult Wuchereria bancrofti in vivo. Trans R Soc Trop Med Hyg 1997 Feb; 91: 78–81
Sabry M, Gamal H, El-Masry, et al. A placebo-controlled double-blind trial for the treatment of bancroftian filariasis with ivermectin or diethylcarbamazine. Trans R Soc Trop Med Hyg 1991; 85: 640–3
Dreyer G, Countinho A, Miranda D, et al. Treatment of bancroftian filariasis in Recife, Brazil: a two year comparative study of the efficacy of single treatment with ivermectin and diethylcarbamazine. Trans R Soc Trop Med Hyg 1993; 48: 178–85
Ottesen EA, Vijayasekaran V, Kumaraswami V, et al. A controlled trial of ivermectin and diethylcarbamazine in lymphatic filariasis. N Engl J Med 1990 Apr; 322: 1113–7
Eberhard ML, Hightower AW, Addiss DG, et al. Clearance of Wuchereria bancrofti antigen after treatment with diethylcarbamazine or ivermectin. Am J Trop Med Hyg 1997 Oct; 57(4): 483–6
Dreyer G. Comparative efficacy of three different diethylcarbamazine regimes in lymphatic filariasis. Trans R Soc Trop Med Hyg 1995 May; 89(3): 319–32
Addiss DG, Eberhard ML, Lammie PJ, et al. Comparative trial of clearing dose and single high dose ivermectin and diethylcarbamazine against Wuchereria bancrofli microfilaraemia. Am J Trop Med Hyg 1993 Feb; 48: 178–85
Ismail MM, Weil GJ, Jayasinghe KS. Prolonged clearance of microfilaraemia inpatients with bancroftian filariasis after multiple high doses of ivermectin of diethlycarbamazine. Trans R Soc Trop Med Hyg 1996 Nov; 90(6): 684–8
Richards FO, Eberhard ML, Bryan RT, et al. Comparison of high dose ivermectin and diethylcarbamazine for activity against bancroftian filariasis in Haiti. Am J Trop Med Hyg 1991; 44: 3–10
Addiss DG, Beach MJ, Streit TG. Randomised placebo-controlled comparison of ivermectin and albendazole alone and in combination for Wuchereria bancrofti microfilaraemia in Haitian children. Lancet 1997 Aug; 350: 480–5
Ismail MM, Jayakody RL, Weil GJ, et al. Efficacy of single dose combinations of albendazole ivermectin and diethylcarbamazine for the treatment of bancrofti filariasis. Trans R Soc Trop Med Hyg 1998 Feb; 92: 94–7
World Health Organization (WHO). The control of schistomiasis: second report of the WHO Expert Committee [technical report series 830]. Geneva: WHO, 1993
Cilio D, Pica-Mattoccia L, Archer S. Antischistosomal drugs: past, present and future. Pharmacol Ther 1995; 68: 35–8
Murray-Smith SQ. A case of refractory schistosomiasis [letter]. Med JAust 1996; 165: 458
Herwaldt BL. Persistence of Schi Stornosorna haematobium infection despite multiple courses of therapy with praziquantel. Clin Infect Dis 20; 309–15
Fallon PG, Doenhoff MJ. Drug resistant schistosomiasis: resistance to praziquantel and oxamniquine induced in Schistosoma mansoni in mice is drug specific. Am J Trop Med Hyg 1994; 51: 83–8
Picquet M. Efficacy of praziquantel against Schistosoma mansoni in northern Senegal. Trans R Soc Trop Med Hyg 1998; 92: 90–3
Stelma FF. Oxamniquine cures Schistosoma mansoni infection in a focus in which cure rates with praziquantel are unusually low. J Infect Dis 1997; 176: 304–7
Guisse F. Therapeutic evaluation of two different dose regimes of praziquantel in a recent Schistosoma mansoni focus in northern Senegal. Am J Trop Med Hyg 1997; 56: 511–14
Ciolio D. Chemotherapy of schistosomiasis: an update. Parasitai Today 1998; 14(10): 418–20
Bennett JL. The development of resistance to antihelmintics: a perspective with an emphasis on the antischistosomal drug praziquantel. Exp Parasitai 1997; 87: 260–2
Ismail M. Characterisation of isolates of Schistosoma mansoni from Egyptian villagers that tolerate high doses of praziquantel. Am J Trop Med Hyg 1996; 55: 214–18
Chen Y, Xu G, Feng Z, et al. Studies on efficacy on praziquantel and mebendazole medicated salt in treatment of Echinochasmus fujianensis infection. Southeast Asia J Trop Med Pub Health 1997 Jun; 28: 344–6
Fan PC, Chung WC, Chan CH, et al. Studies on taeniasis in Taiwan: field trial on evaluation of therapeutic efficacy of mebendazole and praziquantel. Southeast Asia J Trop Med Pub Health 1986 Mar; 17: 82–90
Benjapong W, Naeypatimanond S, Benjapong K, et al. Studies on paragonimiasis: treatment with mebendazole, emetine and praziquantel. Southeast Asia J Trop Med Pub Health 1984 Sep; 15: 354–9
Bout DT, Deslee D, Capron A. Protection against schistosomiasis produced by cyclosporin A. Am J Trop Med Hyg 1984; 33: 185–6
Ekwanzala M, Pepin J, Khonde N, et al. In the heart of darkness: sleeping sickness in Zaire. Lancet 1996; 348: 1427–30
Smith DH, Bailey JW. Human African trypanosomiasis in south eastern Uganda: clinical diversity and isoenzyme profiles. Ann Trop Med Parasitai 1997; 91: 851–6
Smith DH, Pepin J, Stich AHR. Human African trypanosomiasis: an emerging public health crisis. Br Med Bull 1998; 54: 341–55
Pepin J, Milord F, Khonde AN, et al. Gambiense trypanosomiasis: frequency of and risk factors for failure of melarsoprol therapy. Trans R Soc Trop Med Hyg 1994 Aug; 88: 447–52
Pepin J, Milord F, Khonde AN, et al. Risk factors for encephalopathy and mortality during melarsoprol treatment of Trypanosoma brucei gambiense sleeping sickness. Trans R Soc Trop Med Hyg 1995 Feb; 89: 92–7
Pepin J, Milord F, Guern C. Trial of prednisolone for prevention of melarsoprol-induced encephalopathy in gambiense sleeping sickness. Lancet 1989 Jun; I(8649); 1246–50
Doua F, Miezan TW, Sanon JR. The efficacy of pentamidine in the treatment of early-late stage Trypanosoma brucei gambiense sleeping sickness. Am J Trop Med Hyg 1996 Dec; 55: 586–8
Khonde N, Pepin J, Mpia B. A seven day course of eflornithine for relapsing Trypanosoma brucei gambiense sleeping sickness. Trans R Soc Trop Med Hyg 1997 Apr; 91: 212–3
Taelman H, Schechter PJ, Marcelis L, et al. Difluoromethylornithine an effective treatment of Gambian trypanosomiasis. Am J Med 1987 Mar; 82: 607–14
Milord F, Pepin J, Loko L. Efficacy and toxicity of eflornithine for treatment of Trypanosoma brucei gambiense sleeping sickness. Lancet 1992 Sep; 340: 652–5
Milord F, Loko L, Ehier L. Eflornithine concentrations in serum and cerebrospinal fluid of 63 patients treated for Trypanosoma brucei gambiense sleeping sickness. Trans R Soc Trop Med Hyg 1993 Aug; 87: 473–7
Partnership for Child Development. Better health, nutrition and education for the school aged child. Trans R Soc Trop Med Hyg 1994; 88: 344–5
Savoli L, Renganathan E, Montresor A, et al. Control of Schistosomiasis: a global picture. Parasitai Today 1997; 13: 444–50
Ciment J. WHO celebrates triumph over river blindness. BMJ 1999; 319: 1090
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Stephenso, I., Wiselka, M. Drug Treatment of Tropical Parasitic Infections. Drugs 60, 985–995 (2000). https://doi.org/10.2165/00003495-200060050-00002
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DOI: https://doi.org/10.2165/00003495-200060050-00002