Feasibility and safety of mass drug coadministration with azithromycin and ivermectin for the control of neglected tropical diseases: a single-arm intervention trial.

BACKGROUND: Mass drug administration has made a major contribution to the public health control of several important neglected tropical diseases. For settings with more than one endemic disease, combined mass drug administration has potential practical advantages compared with separate programmes but needs confirmation of feasibility and safety. We undertook a study of mass drug administration in the Solomon Islands for trachoma and scabies control using ivermectin and azithromycin, key drugs in the control of neglected tropical diseases worldwide. METHODS: The entire population of Choiseul province, Solomon Islands, was eligible to participate. An azithromycin-based mass drug administration regimen was offered in line with standard recommendations for trachoma elimination (oral azithromycin or topical tetracycline). An ivermectin-based mass drug administration regimen was offered at the same time (oral ivermectin or topical permethrin), with a further dose 7-14 days later, using a modified version of a regimen demonstrated to be effective for scabies control. All participants underwent safety assessments 7-14 days later. Participants in ten randomly selected sentinel villages underwent a more detailed safety assessment. Routine health system reports of hospital or clinic admissions and deaths were also obtained to compare health outcomes in the 12 month period before and after the mass drug administration. FINDINGS: The study enrolled 26 188 participants, 99·3% of the estimated resident population as determined at the 2009 census. Of those enrolled, 25 717 (98·2%) received the trachoma regimen and 25 819 (98·6%) received the first dose of the scabies regimen between Sept 1, and Oct 2, 2015. A second dose of the scabies regimen was received by 21 931 (83·7%) of participants. Adverse events, all mild and transient, were recorded in 571 (2·6%) of the entire study population and 58 (4·1%) of participants in the ten sentinel villages. In the 12 months before and after the mass drug administration the numbers of hospital admissions (1530 vs 1602) and deaths (73 vs 83) were similar. In the month after the mass drug administration, 84 individuals were admitted to hospital and two died, compared with a monthly median of 116 admissions (IQR 106-159) and six deaths (IQR 4-7) in the 12 months before and after the mass drug administration. INTERPRETATION: In the largest trial so far involving coadministration of regimens based on ivermectin and azithromycin, the combination was safe and feasible in a population of more than 26 000 people. Coadministration of mass drug administration based on these two drugs opens up new potential for the control of neglected tropical diseases. FUNDING: International Trachoma Initiative, Murdoch Children's Research Institute, Scobie and Claire Mackinnon Trust, Wellcome Trust

Efficacy of mass drug administration with ivermectin for control of scabies and impetigo, with coadministration of azithromycin: a single-arm community intervention trial.

BACKGROUND: In small community-based trials, mass drug administration of ivermectin has been shown to substantially decrease the prevalence of both scabies and secondary impetigo; however, their effect at large scale is untested. Additionally, combined mass administration of drugs for two or more neglected diseases has potential practical advantages, but efficacy of potential combinations should be confirmed. METHODS: The azithromycin ivermectin mass drug administration (AIM) trial was a prospective, single-arm, before-and-after, community intervention study to assess the efficacy of mass drug administration of ivermectin for scabies and impetigo, with coadministration of azithromycin for trachoma. Mass drug administration was offered to the entire population of Choiseul Province, Solomon Islands, and of this population we randomly selected two sets of ten sentinel villages for monitoring, one at baseline and the other at 12 months. Participants were offered a single dose of 20 mg/kg azithromycin, using weight-based bands. Children weighing less than 12·5 kg received azithromycin oral suspension (20 mg/kg), and infants younger than 6 months received topical 1% tetracycline ointment. For ivermectin, participants were offered two doses of oral ivermectin 200 μg/kg 7-14 days apart using weight-based bands, or 5% permethrin cream 7-14 days apart if ivermectin was contraindicated. Our study had the primary outcomes of safety and feasibility of large-scale mass coadministration of oral ivermectin and azithromycin, which have been previously reported. We report here the prevalence of scabies and impetigo in residents of the ten baseline villages compared with those in the ten 12-month villages, as measured by examination of the skin, which was a secondary outcome of the trial. Further outcomes were comparison of the number of all-cause outpatient attendances at government clinics in Choiseul Province at various timepoints before and after mass drug administration. The trial was registered with the Australian and New Zealand Trials Registry (ACTRN12615001199505). FINDINGS: During September, 2015, over 4 weeks, 26 188 people (99·3% of the estimated population of Choiseul [n=26 372] as determined at the 2009 census) were treated. At baseline, 1399 (84·2%) of 1662 people living in the first ten villages had their skin examined, of whom 261 (18·7%) had scabies and 347 (24·8%) had impetigo. At 12 months after mass drug administration, 1261 (77·6%) of 1625 people in the second set of ten villages had their skin examined, of whom 29 (2·3%) had scabies (relative reduction 88%, 95% CI 76·5-99·3) and 81 (6·4%) had impetigo (relative reduction 74%, 63·4-84·7). In the 3 months after mass drug administration, 10 614 attended outpatient clinics for any reason compared with 16 602 in the 3 months before administration (decrease of 36·1%, 95% CI 34·7-37·6), and during this period attendance for skin sores, boils, and abscesses decreased by 50·9% (95% CI 48·6-53·1). INTERPRETATION: Ivermectin-based mass drug administration can be scaled to a population of over 25 000 with high efficacy and this level of efficacy can be achieved when mass drug administration for scabies is integrated with mass drug administration of azithromycin for trachoma. These findings will contribute to development of population-level control strategies. Further research is needed to assess durability and scalability of mass drug administration in larger, non-island populations, and to assess its effect on the severe bacterial complications of scabies. FUNDING: International Trachoma Initiative, Murdoch Children's Research Institute, Scobie and Claire Mackinnon Trust, and the Wellcome Trust

Feasibility and safety of mass drug coadministration with azithromycin and ivermectin for the control of neglected tropical diseases: a single-arm intervention trial

Summary: Background: Mass drug administration has made a major contribution to the public health control of several important neglected tropical diseases. For settings with more than one endemic disease, combined mass drug administration has potential practical advantages compared with separate programmes but needs confirmation of feasibility and safety. We undertook a study of mass drug administration in the Solomon Islands for trachoma and scabies control using ivermectin and azithromycin, key drugs in the control of neglected tropical diseases worldwide. Methods: The entire population of Choiseul province, Solomon Islands, was eligible to participate. An azithromycin-based mass drug administration regimen was offered in line with standard recommendations for trachoma elimination (oral azithromycin or topical tetracycline). An ivermectin-based mass drug administration regimen was offered at the same time (oral ivermectin or topical permethrin), with a further dose 7–14 days later, using a modified version of a regimen demonstrated to be effective for scabies control. All participants underwent safety assessments 7–14 days later. Participants in ten randomly selected sentinel villages underwent a more detailed safety assessment. Routine health system reports of hospital or clinic admissions and deaths were also obtained to compare health outcomes in the 12 month period before and after the mass drug administration. Findings: The study enrolled 26 188 participants, 99·3% of the estimated resident population as determined at the 2009 census. Of those enrolled, 25 717 (98·2%) received the trachoma regimen and 25 819 (98·6%) received the first dose of the scabies regimen between Sept 1, and Oct 2, 2015. A second dose of the scabies regimen was received by 21 931 (83·7%) of participants. Adverse events, all mild and transient, were recorded in 571 (2·6%) of the entire study population and 58 (4·1%) of participants in the ten sentinel villages. In the 12 months before and after the mass drug administration the numbers of hospital admissions (1530 vs 1602) and deaths (73 vs 83) were similar. In the month after the mass drug administration, 84 individuals were admitted to hospital and two died, compared with a monthly median of 116 admissions (IQR 106–159) and six deaths (IQR 4–7) in the 12 months before and after the mass drug administration. Interpretation: In the largest trial so far involving coadministration of regimens based on ivermectin and azithromycin, the combination was safe and feasible in a population of more than 26 000 people. Coadministration of mass drug administration based on these two drugs opens up new potential for the control of neglected tropical diseases. Funding: International Trachoma Initiative, Murdoch Children's Research Institute, Scobie and Claire Mackinnon Trust, Wellcome Trust