1 3 Effects of albendazole on the clinical outcome and immunological 4 responses in helminth co-infected tuberculosis patients: a double blind 5 randomised clinical trial 6 7 8 E. Abate a,b,⇑ Q1 , D. Elias c , A. Getachew d , S. Alemu e , E. Diro e , S. Britton f , A. Aseffa g , O. Stendahl b , 9 T. Schön b,h 10 a Department of Immunology and Molecular Biology, University of Gondar, Gondar, Ethiopia 11 b Department of Medical Microbiology, Linköping University, Sweden 12 c University of Southern Denmark, Institute of Molecular Medicine, Department of Cancer and Inflammation, Odense, Denmark 13 d Department of Radiology, University of Gondar, Gondar, Ethiopia 14 e Department of Internal Medicine, University of Gondar, Gondar, Ethiopia 15 f Department of Infectious Diseases, Karolinska Hospital, Stockholm, Sweden 16 g Armauer Hansen Research Institute, Addis Ababa, Ethiopia 17 h Department of Clinical Microbiology and Infectious Diseases, Kalmar County Hospital, Kalmar, Sweden 18 19 20 22 article info 23 Article history: 24 Received 17 July 2014 25 Received in revised form 15 September 26 2014 27 Accepted 19 September 2014 28 Available online xxxx 29 Keywords: 30 Helminth 31 Tuberculosis 32 Albendazole 33 Deworming 34 HIV 35 Ethiopia 36 37 abstract 38 Despite several review papers and experimental studies concerning the impact of chronic helminth infec- 39 tion on tuberculosis in recent years, there is a scarcity of data from clinical field studies in highly endemic 40 areas for these diseases. We believe this is the first randomised clinical trial investigating the impact of 41 albendazole treatment on the clinical and immunological outcomes of helminth co-infected tuberculosis 42 patients. A randomised, double-blind, placebo-controlled trial of albendazole (400 mg per day for 3 days) 43 in helminth-positive tuberculosis patients was conducted in Gondar, Ethiopia. The primary outcome was 44 clinical improvement (DTB score) after 2 months. Among secondary outcomes were changes in the levels 45 of eosinophils, CD4+ T cells, regulatory T cells, IFN-c, IL-5 and IL-10 after 3 months. A total of 140 46 helminth co-infected tuberculosis patients were included with an HIV co-infection rate of 22.8%. There 47 was no significant effect on the primary outcome (DTB score: 5.6 ± 2.9 for albendazole versus 5.9 ± 2.5 48 for placebo, P = 0.59). The albendazole-treated group showed a decline in eosinophil cells (P = 0.001) 49 and IL-10 (P = 0.017) after 3 months. In an exploratory analysis after 12 weeks, the albendazole treated 50 group showed a trend towards weight gain compared with the placebo group (11.2 ± 8.5 kg versus 51 8.2 ± 8.7 kg, P = 0.08)). The reductions in eosinophil counts and IL-10 show that asymptomatic helminth 52 infection significantly affects host immunity during tuberculosis and can be effectively reversed by 53 albendazole treatment. The clinical effects of helminth infection on chronic infectious diseases such as 54 tuberculosis merit further characterisation. 55 Ó 2014 Published by Elsevier Ltd. on behalf of Australian Society for Parasitology Inc. 56 57 58 59 1. Introduction 60 Similar to tuberculosis (TB), it has been estimated that one- 61 third of the global human population is infected with intestinal 62 parasites (World Health Organization (WHO), 2012; Salgame 63 et al., 2013). Several studies, including some from Ethiopia, have 64 shown an increased rate of helminth infection in TB patients com- 65 pared with household contacts living in the same room with active 66 TB patients and the healthy population (Tristão-Sá et al., 2002; 67 Abate et al., 2012). The impact of helminth infection on the risk 68 of developing TB and during the course of active TB is not well 69 understood but is believed to involve helminth-induced effects 70 on cell mediated immunity (Bentwich et al., 1999; Borkow et al., 71 2001; Elias et al., 2006). 72 Protective immunity in TB has been shown to be dependent on 73 T-helper 1 (Th1) CD4+ T cells producing IFN-c and TNF-a, as well 74 as cytolytic T cells (CTLs) producing granule-associated cytolytic 75 effector molecules (Brighenti and Andersson, 2012). It has been 76 postulated that helminth co-infection could modulate the protec- 77 tive Th1-response against TB through an effect on the Th1/Th2 78 balance, with increased Th2 dominance and activity of regulatory http://dx.doi.org/10.1016/j.ijpara.2014.09.006 0020-7519/Ó 2014 Published by Elsevier Ltd. on behalf of Australian Society for Parasitology Inc. ⇑ Corresponding author at: Department of Immunology and Molecular Biology, University of Gondar, P.O. Box 1353, Gondar, Ethiopia. Tel.: +251 911 464024; fax: +251 058 114 1240/058 111 1479. E-mail address: ebbaabate@yahoo.com (E. Abate). International Journal for Parasitology xxx (2014) xxx–xxx Contents lists available at ScienceDirect International Journal for Parasitology journal homepage: www.elsevier.com/locate/ijpara PARA 3717 No. of Pages 8, Model 5G 9 December 2014 Please cite this article in press as: Abate, E., et al. Effects of albendazole on the clinical outcome and immunological responses in helminth co-infected tuberculosis patients: a double blind randomised clinical trial. Int. J. Parasitol. (2014), http://dx.doi.org/10.1016/j.ijpara.2014.09.006