Update on Treatment and Resistance of Human Trichuriasis

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Mireku MO, Boivin MJ, Davidson LL, Ouedraogo S, Koura GK, Alao MJ, et al. Impact of helminth infection during pregnancy on cognitive and motor functions of one-year-old children. PLoS Negl Trop Dis. 2015;9:e0003463.

Elliott AM, Namujju PB, Mawa PA, Quigley MA, Nampijja M, Nkurunziza PM, et al. A randomised controlled trial of the effects of albendazole in pregnancy on maternal responses to mycobacterial antigens and infant responses to Bacille Calmette-Guerin (BCG) immunisation [ISRCTN32849447]. BMC Infect Dis. 2005;5:115.

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Esen M, Mordmuller B, de Salazar PM, Adegnika AA, Agnandji ST, Schaumburg F, et al. Reduced antibody responses against Plasmodium falciparum vaccine candidate antigens in the presence of Trichuris trichiura. Vaccine. 2012;30:7621–4.

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Adegnika AA, Zinsou JF, Issifou S, Ateba-Ngoa U, Kassa RF, Feugap EN, et al. Randomized, controlled, assessor-blind clinical trial to assess the efficacy of single- versus repeated-dose albendazole to treat ascaris lumbricoides, trichuris trichiura, and hookworm infection. Antimicrob Agents Chemother. 2014;58:2535–40. This randomized controlled clinical trial assesses single dose versus repeated-dose albendazole treatment for STH including T. trichirua. Three day albendazol treatment was significantly more efficacious than single dose treatment.

Speich B, Ame SM, Ali SM, Alles R, Huwyler J, Hattendorf J, et al. Oxantel pamoate-albendazole for Trichuris trichiura infection. N Engl J Med. 2014;370:610–20. This randomized controlled clinical trial assessed the efficacy of oxantel pamoat-albendazol combination agains T. trichiura compared to mebendazol therapy. Cure rate was higher although still disappointingly low at 31.2%.

Namwanje H, Kabatereine N, Olsen A. A randomised controlled clinical trial on the safety of co-administration of albendazole, ivermectin and praziquantel in infected schoolchildren in Uganda. Trans RSoc Trop Med Hyg. 2011;105:181–8.

Samuel F, Degarege A, Erko B. Efficacy and side effects of albendazole currently in use against Ascaris, Trichuris and hookworm among school children in Wondo Genet, southern Ethiopia. Parasitol Int. 2014;63:450–5. Single dose albendazole treatment of T. trichiura was associated with 31% cure rate in ths clincial trial conducted in Ethiopia.

Speich B, Ame SM, Ali SM, Alles R, Hattendorf J, Utzinger J, et al. Efficacy and safety of nitazoxanide, albendazole, and nitazoxanide-albendazole against Trichuris trichiura infection: a randomized controlled trial. PLoS Negl Trop Dis. 2012;6:e1685. Nitazoxanide was assessed in comparison with albendazole and nitazoxanide-albendazole combination in a randomized controlled clinical trial. Nitazoxanide proved to be ineffective against T. trichiura with a cure rate of only 7%.

Yap P, Du ZW, Wu FW, Jiang JY, Chen R, Zhou XN, et al. Rapid re-infection with soil-transmitted helminths after triple-dose albendazole treatment of school-aged children in Yunnan, People’s Republic of China. Am J Trop Med Hyg. 2013;89:23–31. Three day treatment of T. trichiura with albendazole led to 20% cure rate in this Chinese population. Re-infection with T. trichiura was slower than for other STH.

Geary TG. Are new anthelmintics needed to eliminate human helminthiases? Curr Opin Infect Dis. 2012;25:709–17.

Mpairwe H, Tweyongyere R, Elliott A. Pregnancy and helminth infections. Parasite Immunol. 2014;36:328–37.

Speich B, Ali SM, Ame SM, Bogoch II, Alles R, Huwyler J, et al. Efficacy and safety of albendazole plus ivermectin, albendazole plus mebendazole, albendazole plus oxantel pamoate, and mebendazole alone against Trichuris trichiura and concomitant soil-transmitted helminth infections: a four-arm, randomised controlled trial. Lancet Infect Dis. 2015;15:277–84. A four arm head-to -head comparison of combinations therapies for T. trichiura demonstrated that albendazole in combination with oxantel pamoate leads to highest cure rates.

Adams EJ, Stephenson LS, Latham MC, Kinoti SN. Physical activity and growth of Kenyan school children with hookworm, Trichuris trichiura and Ascaris lumbricoides infections are improved after treatment with albendazole. J Nutr. 1994;124:1199–206.

Stephenson LS, Latham MC, Adams EJ, Kinoti SN, Pertet A. Physical fitness, growth and appetite of Kenyan school boys with hookworm, Trichuris trichiura and Ascaris lumbricoides infections are improved four months after a single dose of albendazole. J Nutr. 1993;123:1036–46.

Stephenson LS, Latham MC, Adams EJ, Kinoti SN, Pertet A. Weight gain of Kenyan school 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.

Elliott AM, Ndibazza J, Mpairwe H, Muhangi L, Webb EL, Kizito D, et al. Treatment with anthelminthics during pregnancy: what gains and what risks for the mother and child? Parasitology. 2011;138:1499–507.

Ndibazza J, Mpairwe H, Webb EL, Mawa PA, Nampijja M, Muhangi L, et al. Impact of anthelminthic treatment in pregnancy and childhood on immunisations, infections and eczema in childhood: a randomised controlled trial. PLoS One. 2012;7:e50325.

Mpairwe H, Webb EL, Muhangi L, Ndibazza J, Akishule D, Nampijja M, et al. Anthelminthic treatment during pregnancy is associated with increased risk of infantile eczema: randomised-controlled trial results. Pediatr Allergy Immunol. 2011;22:305–12.

Webb EL, Mawa PA, Ndibazza J, Kizito D, Namatovu A, Kyosiimire-Lugemwa J, et al. Effect of single-dose anthelmintic treatment during pregnancy on an infant’s response to immunisation and on susceptibility to infectious diseases in infancy: a randomised, double-blind, placebo-controlled trial. Lancet. 2011;377:52–62.

Atukorala TM, de Silva LD, Dechering WH, Dassenaeike TS, Perera RS. Evaluation of effectiveness of iron-folate supplementation and anthelminthic therapy against anemia in pregnancy—a study in the plantation sector of Sri Lanka. Am J Clin Nutr. 1994;60:286–92.

de Silva NR, Sirisena JL, Gunasekera DP, Ismail MM, de Silva HJ. Effect of mebendazole therapy during pregnancy on birth outcome. Lancet. 1999;353:1145–9.

Torlesse H, Hodges M. Albendazole therapy and reduced decline in haemoglobin concentration during pregnancy (Sierra Leone). Trans RSoc Trop Med Hyg. 2001;95:195–201.

Torlesse H, Hodges M. Anthelminthic treatment and haemoglobin concentrations during pregnancy. Lancet. 2000;356:1083.

Levecke B, Montresor A, Albonico M, Ame SM, Behnke JM, Bethony JM, et al. Assessment of anthelmintic efficacy of mebendazole in school children in six countries where soil-transmitted helminths are endemic. PLoS Negl Trop Dis. 2014;8:e3204. This analysis of multiple trials assessing mebendazole and albendazole for egg reduction in T. trichiura demonstrated equal egg reduction rates for mebendazole and albendazole.

Namwanje H, Kabatereine NB, Olsen A. Efficacy of single and double doses of albendazole and mebendazole alone and in combination in the treatment of Trichuris trichiura in school-age children in Uganda. Trans RSoc Trop Med Hyg. 2011;105:586–90. This clinical trial evaluated the impact of doubling the dose of benzimidazole therapy for T. trichiura. The main finding is an increased efficacy of double dose treatment and of combination of mebendazole with albendazole.

Steinmann P, Utzinger J, Du ZW, Jiang JY, Chen JX, Hattendorf J, et al. Efficacy of single-dose and triple-dose albendazole and mebendazole against soil-transmitted helminths and Taenia spp.: a randomized controlled trial. PLoS One. 2011;6:e25003. This study assessed the efficacy of benzimidazole therapy against STH when given as single dose or triple dose regimens. Triple dose regimens were more efficacious against T. trichiura.

Lacey E. Mode of action of benzimidazoles. Parasitol Today. 1990;6:112–5.

Wolstenholme AJ, Fairweather I, Prichard R, von Samson-Himmelstjerna G, Sangster NC. Drug resistance in veterinary helminths. Trends Parasitol. 2004;20:469–76.

Demeler J, Kruger N, Krucken J, von der Heyden VC, Ramunke S, Kuttler U, et al. Phylogenetic characterization of beta-tubulins and development of pyrosequencing assays for benzimidazole resistance in cattle nematodes. PLoS One. 2013;8:e70212.

Diawara A, Drake LJ, Suswillo RR, Kihara J, Bundy DA, Scott ME, et al. Assays to detect beta-tubulin codon 200 polymorphism in Trichuris trichiura and Ascaris lumbricoides. PLoS Negl Trop Dis. 2009;3:e397. This study describes pyroseuqencing assays for the detection of molecular markers of benzimidazole resistance. Assays were employed in treatment naive populationas and in populations with intensive mass treatments and the authors discuss the implications of detected resistance markers.