The safety of combined triple drug therapy with ivermectin, diethylcarbamazine and albendazole in the neglected tropical diseases co-endemic setting of Fiji: A cluster randomised trial

Hardy, Myra; Samuela, Josaia; Kama, Mike; Tuicakau, Meciusela; Romani, Lucia; Whitfeld, Margot; King, Christopher L.; Weil, Gary J.; Grobler, Anneke; Robinson, Leanne J.; Kaldor, John; Steer, Andrew C.

doi:10.1371/journal.pntd.0008106

Cited by 22 publications

(27 citation statements)

References 19 publications

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“…There were issues with coordinating every island within the four divisions, and maintaining a consistent MDA availability across the entire division was a challenge as was the level of participation. Efforts intensified after 2007, but continuing transmission led to more MDA rounds in the face of continuing transmission, and the testing of triple drug MDA in the Eastern Division in 2018 [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

Lymphatic filariasis in Fiji: progress towards elimination, 1997–2007

et al. 2020

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Background Lymphatic filariasis (LF) is a major public health problem in the Pacific Region, including in Fiji. Through transmission by the mosquito vector Aedes, Fiji has suffered the burden of remaining endemic with LF despite efforts at elimination prior to 1999. In the year 1999, Fiji agreed to take part in the Pacific Programme for Elimination of LF (PacELF) and the Global Programme to Eliminate LF. Methods This study reviewed and collated past data on LF in Fiji between 1997 and 2007. Sources included published papers as well as unpublished PacELF and WHO program meeting and survey reports. Records were held at Fiji’s Department of Health and Medical Services, James Cook University and the WHO office in Suva, Fiji. Results Baseline surveys between 1997 and 2002 showed that Fiji was highly endemic for LF with an estimated 16.6% of the population antigen positive and 6.3% microfilaria positive at that time. Five rounds of annual mass drug administration (MDA) using albendazole and diethylcarbamazine commenced in 2002. Programmatic coverage reported was 58–70% per year, but an independent coverage survey in 2006 in Northern Division after the fifth MDA suggested that actual coverage may have been higher. Monitoring of the program consisted of antigen prevalence surveys in all ages with sentinel and spot check surveys carried out in 2002 (pre MDA), 2004, and 2005, together with knowledge, attitude, and practice surveys. The stop-MDA survey (C survey) in 2007 was a nationwide stratified cluster survey of all ages according to PacELF guidelines, designed to sample by administrative division to identify areas still needing MDA. The national antigen prevalence in 2007 was reduced by more than a third to 9.5%, ranging from 0.9% in Western Division to 15.4% in Eastern Division, while microfilaria prevalence was reduced by almost four-fifths to 1.4%. Having not reached the target threshold of 1% prevalence in all ages, Fiji wisely decided to continue MDA after 2007 but to move from nationwide implementation to four (later five) separate evaluation units with independent timelines using global guidelines, building on program experience to put more emphasis on increasing coverage through prioritized communication strategies, community participation, and morbidity alleviation. Conclusion Fiji conducted nationwide MDA for LF annually between 2002 and 2006, monitored by extensive surveys of prevalence, knowledge, and coverage. From a high baseline prevalence in all divisions, large reductions in overall and age-specific prevalence were achieved, especially in the prevalence of microfilariae, but the threshold for stopping MDA was not reached. Fiji has a large rural and geographically widespread population, program management was not consistent over this period, and coverage achieved was likely not optimal in all areas. After learning from these many challenges and activities, Fiji was able to build on the progress achieved and the heterogeneity observed in prevalence to realign towards a more stratified and improved program after 2007. The information presented here will assist the country to progress towards validating elimination in subsequent years.

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Section: Discussionmentioning

confidence: 99%

Lymphatic filariasis in Fiji: progress towards elimination, 1997–2007

et al. 2020

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“…Ivermectin has a short half-life of 12–56 hours and is not ovicidal; therefore, a repeat treatment is recommended once the eggs have hatched. Two studies are currently underway in the Solomon Islands and Fiji to assess if a single dose of ivermectin is as effective as two doses 46 , 47 .…”

Section: Treatment For Scabiesmentioning

confidence: 99%

“…NTDs are a priority for the WHO. Owing to the effectiveness of ivermectin against a number of these NTDs, there is support for ivermectin-based MDA to be designed to treat multiple diseases at once 47 .…”

Section: Mass Drug Administrationmentioning

confidence: 99%

Recent advances in understanding and treating scabies

Welch¹,

Romani²,

Whitfeld³

2021

Fac Rev

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Scabies is an infestation of the skin caused by the mite Sarcoptes scabiei. In 2017, scabies was recognised by the World Health Organisation as a disease of public importance and was consequently added to the list of neglected tropical diseases. An estimated 200 million people currently have scabies worldwide. Scabies is endemic in many developing countries, with the highest prevalence being in hot, humid climates such as the Pacific and Latin American regions. Scabies causes a host immune response which is intensely itchy. Scratching of the lesions can lead to secondary bacterial infections of the skin, such as impetigo, most commonly caused by Streptococcus pyogenes or Staphylococcus aureus . This can have fatal consequences, such as septicaemia, glomerulonephritis, and rheumatic heart disease. Advances over the past 5 years indicate that mass drug administration is an effective strategy to treat scabies. This review will outline advances in the mite biology, epidemiological understanding, diagnosis, and treatment of scabies.

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“…However, results from extensive clinical trials are required before we know if ivermectin could work for patients. Also, the combination of ivermectin with other medications that are currently being used might result in a more‐favorable prognosis for ovarian cancer patients 48 . Obviously, the detailed molecular mechanisms of this multi‐functional ivermectin must be clarified.…”

Section: Discussionmentioning

confidence: 99%

SILAC quantitative proteomics analysis of ivermectin‐related proteomic profiling and molecular network alterations in human ovarian cancer cells

Desiderio

et al. 2020

J Mass Spectrom

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The antiparasitic agent ivermectin offers more promises to treat a diverse range of diseases. However, a comprehensive proteomic analysis of ivermectin‐treated ovarian cancer (OC) cells has not been performed. This study sought to identify ivermectin‐related proteomic profiling and molecular network alterations in human OC cells. Stable isotope labeling with amino acids in cell culture (SILAC)‐based quantitative proteomics was used to study the human OC TOV‐21G cells. After TOV‐21G cells underwent 10 passages in SILAC‐labeled growth media, TOV‐21G cells were treated with 10 ml of 20 μmol/L ivermectin in cell growing medium for 24 h. The SILAC‐labeled proteins were digested with trypsin; tryptic peptides were identified with mass spectrometry (MS). Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was used to mine signaling pathway alterations with ivermectin‐related proteins in TOV‐21G cells. Gene ontology (GO) analysis was used to explore biological functions of ivermectin‐related proteins, including biological processes (BPs), cellular components (CCs), and molecular functions (MFs). The protein‐protein interaction network was analyzed with molecular complex detection (MCODE) to identify hub modules. In total, 4,447 proteins were identified in ivermectin‐treated TOV‐21G cells. KEGG analysis revealed 89 statistically significant signaling pathways. Interestingly, the clustering analysis of these pathways showed that ivermectin was involved in various cancer pathogenesis processes, including modulation of replication, RNA metabolism, and translational machinery. GO analysis revealed 69 statistically significant CCs, 87 MFs, and 62 BPs. Furthermore, MCODE analysis identified five hub modules, including 147 hub molecules. Those hub modules involved ribosomal proteins, RNA‐binding proteins, cell‐cycle progression‐related proteins, proteasome subunits, and minichromosome maintenance proteins. These findings demonstrate that SILAC quantitative proteomics is an effective method to analyze ivermectin‐treated cells, provide the first ivermectin‐related proteomic profiling and molecular network alterations in human OC cells, and provide deeper insights into molecular mechanisms and functions of ivermectin to inhibit OC cells.

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The safety of combined triple drug therapy with ivermectin, diethylcarbamazine and albendazole in the neglected tropical diseases co-endemic setting of Fiji: A cluster randomised trial

Cited by 22 publications

References 19 publications

Lymphatic filariasis in Fiji: progress towards elimination, 1997–2007

Lymphatic filariasis in Fiji: progress towards elimination, 1997–2007

Recent advances in understanding and treating scabies

SILAC quantitative proteomics analysis of ivermectin‐related proteomic profiling and molecular network alterations in human ovarian cancer cells

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