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

Abstract

SummaryBackgroundMass 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.MethodsThe 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.FindingsThe 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.InterpretationIn 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.FundingInternational Trachoma Initiative, Murdoch Children's Research Institute, Scobie and Claire Mackinnon Trust, Wellcome Trust.

Classic and Non-classic (Surrepticius) Scabies: Diagnostic and Treatment Considerations

“…Indeed, Streptococcal infection can subsequently result in rheumatic fever (and rheumatic heart disease) or post-streptococcal glomerulonephritis; both bacteria can also result in cellulitis and sepsis. Therefore, coadministration of oral antibiotics with topical and/or oral scabies therapy may be warranted [3,17,20].…”

The public health control of scabies: priorities for research and action

“…In addition to the long-standing practice of co-administration with albendazole, large-scale studies have now demonstrated the safety of co-administration with azithromycin, opening the possibility of integrating control of scabies with control of yaws and/or trachoma. [128][129][130] Similarly, early analysis of a multi-national safety cohort study of combination therapy of ivermectin, diethylcarbamazine and albendazole (IDA) for lymphatic filariasis did not reveal safety concerns and administration of this combination of agents has now been recommended for specific epidemiological contexts within WHO guidelines. [131][132][133][134] Monitoring for development of resistance of mites to acaricides will also be important.…”

Control Strategies for Scabies

“…A before-and-after study evaluated a single round of ivermectin-based MDA, offered to a population of 26,000, in combination with azithromycin MDA for trachoma control. The co-administration was well tolerated with no serious adverse events [ 36 ]. A smaller study, from a different region of the Solomon Islands, reported a reduction in scabies prevalence of greater than 90%, 12 months after ivermectin-based MDA [ 37 ].…”

“…There are a number of opportunities for integration of scabies control with other NTDs, especially around the use of ivermectin [ 71 , 72 ]. Examples include successful co-mapping of scabies prevalence with other NTDs [ 17 , 73 ], and co-administration of ivermectin and azithromycin MDA with evaluation of multiple endpoints [ 36 , 37 ]. The roll-out of triple therapy (ivermectin, diethylcarbamazine, and albendazole) for the control of lymphatic filariasis [ 74 , 75 ] presents further opportunities to integrate evaluation of impact of this strategy on scabies.…”