PMID- 35024646
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220430
IS  - 2666-6065 (Electronic)
IS  - 2666-6065 (Linking)
VI  - 18
DP  - 2022 Jan
TI  - Safety of mass drug coadministration with ivermectin, diethylcarbamazine, 
      albendazole, and azithromycin for the integrated treatment of neglected tropical 
      diseases: a cluster randomized community trial.
PG  - 100293
LID - 10.1016/j.lanwpc.2021.100293 [doi]
LID - 100293
AB  - INTRODUCTION: Neglected tropical diseases control programmes run separately. For 
      settings with more than one endemic disease, combined mass drug administration 
      (MDA) has potential practical advantages compared with separate programmes but 
      needs confirmation of safety. We assessed the safety of combined MDA for multiple 
      neglected tropical diseases using ivermectin, diethylcarbamazine, albendazole 
      (IDA) and azithromycin (AZI). METHODS: We conducted an open-label, 
      cluster-randomized trial involving individuals living in 34 wards (smaller 
      administrative division) in two study sites, Namatanai District and Lihir Island, 
      Papua New Guinea. We randomly assigned wards to the combined treatment arm (which 
      received a single dose of the triple combination IDA and a single dose of AZI at 
      the same visit) or the control arm (which received IDA separately followed by AZI 
      separately one week after). All participants underwent safety assessments one day 
      after drug administration. Methodology for collecting the adverse events (AEs) 
      was a general question (in Namatanai) and individual questions about specific AEs 
      (in Lihir). The primary endpoint was the prevalence of AEs. Safety of combined 
      treatment was taken to be non-inferior to that of IDA if the upper limit of the 
      two-sided CI for the difference in rates was equal or lower than 5%. FINDINGS: 
      The study enrolled 15,656 participants. Of those enrolled, 7,281 (46.3%) received 
      the combined regimen and 8,375 (53.3%) received standard treatment with IDA for 
      lymphatic filariasis between Nov 1, 2018, and Apr 15, 2019. Of the individuals in 
      the control group, 4,228 (50.5%) attended a second visit one week apart to 
      receive AZI for yaws. In Namatanai, the proportion of AEs was similar in the 
      combined group (0.8%) compared to the IDA group (1.3%, difference 0.5% [95CI 
      -2.5% to 1.4%]) or the AZI group (3.6%, d -2.8% [95CI -8.6% to 2.8%]). In Lihir, 
      the proportion of AEs was higher in the combined group (23.0%) compared to the 
      IDA group (12.2%, d 10.8% [95% CI 1.5% to 20.2%]) or the AZI group (11.1%, d 
      11.9% [95% CI 2.7% to 21.1%]).We observed 21 (0.3%) grade-2 AEs in the combined 
      treatment group, 33 (0.4%) in the IDA separately group, and 18 (0.2%) in the AZI 
      separately group. No participants required treatment for any AE. We observed no 
      deaths, serious AEs, or AEs of special interest. INTERPRETATION: In the largest 
      trial so far involving coadministration of regimens based on IDA and AZI, the 
      combination was safe and feasible in a population of more than 15,000 people. 
      Combined MDA based on these two regimens opens up new potential for the control 
      of neglected tropical diseases in the Western Pacific region.
CI  - (c) 2021 The Authors.
FAU - John, Lucy N
AU  - John LN
AD  - National Department of Health - Aopi Centre, Port Moresby, Papua New Guinea.
AD  - Barcelona Institute for Global Health - Faculty of Medicine, University of 
      Barcelona, Barcelona, Spain.
AD  - Fight AIDS and Infectious Diseases Foundation, Hospital Germans Trias Pujol, 
      Badalona, Catalonia (Spain).
AD  - School of Medicine and Health Sciences, University of Papua New Guinea, Port 
      Moresby, Papua New Guinea.
FAU - Gonzalez-Beiras, Camila
AU  - Gonzalez-Beiras C
AD  - Fight AIDS and Infectious Diseases Foundation, Hospital Germans Trias Pujol, 
      Badalona, Catalonia (Spain).
FAU - Vall-Mayans, Marti
AU  - Vall-Mayans M
AD  - Fight AIDS and Infectious Diseases Foundation, Hospital Germans Trias Pujol, 
      Badalona, Catalonia (Spain).
FAU - Kolmau, Reman
AU  - Kolmau R
AD  - Lihir Medical Centre, International SOS, Lihir Island, Papua New Guinea.
FAU - Houinei, Wendy
AU  - Houinei W
AD  - National Department of Health - Aopi Centre, Port Moresby, Papua New Guinea.
FAU - Wangi, James
AU  - Wangi J
AD  - WHO PNG Office - Aopi Centre, Port Moresby, Papua New Guinea.
FAU - Marks, Michael
AU  - Marks M
AD  - London School of Hygiene and Tropical Medicine, London, United Kingdom.
AD  - Hospital for Tropical Diseases, London, United Kingdom.
AD  - Division of Infection and Immunity, University College London, London, United 
      Kingdom.
FAU - Mitja, Oriol
AU  - Mitja O
AD  - Fight AIDS and Infectious Diseases Foundation, Hospital Germans Trias Pujol, 
      Badalona, Catalonia (Spain).
AD  - School of Medicine and Health Sciences, University of Papua New Guinea, Port 
      Moresby, Papua New Guinea.
AD  - Lihir Medical Centre, International SOS, Lihir Island, Papua New Guinea.
LA  - eng
PT  - Journal Article
DEP - 20211102
PL  - England
TA  - Lancet Reg Health West Pac
JT  - The Lancet regional health. Western Pacific
JID - 101774968
PMC - PMC8661048
OTO - NOTNLM
OT  - co-administration
OT  - integration
OT  - lymphatic filariasis
OT  - mass drug administration
OT  - safety
OT  - trachoma
OT  - yaws
COIS- We declare no competing interests.
EDAT- 2022/01/14 06:00
MHDA- 2022/01/14 06:01
PMCR- 2021/11/02
CRDT- 2022/01/13 12:36
PHST- 2021/08/01 00:00 [received]
PHST- 2021/08/25 00:00 [revised]
PHST- 2021/09/15 00:00 [accepted]
PHST- 2022/01/13 12:36 [entrez]
PHST- 2022/01/14 06:00 [pubmed]
PHST- 2022/01/14 06:01 [medline]
PHST- 2021/11/02 00:00 [pmc-release]
AID - S2666-6065(21)00202-9 [pii]
AID - 100293 [pii]
AID - 10.1016/j.lanwpc.2021.100293 [doi]
PST - epublish
SO  - Lancet Reg Health West Pac. 2021 Nov 2;18:100293. doi: 
      10.1016/j.lanwpc.2021.100293. eCollection 2022 Jan.