zithromax and Elephantiasis--Filarial

Traditionally, health ministries implement mass drug administration programmes for each neglected tropical disease (NTD) as separate and distinct campaigns. Many NTDs have overlapping endemicity suggesting co-administration might improve programme reach and efficiency, helping accelerate progress towards 2030 targets. Safety data are required to support a recommendation to undertake co-administration.. We aimed to compile and summarize existing data on co-administration of ivermectin, albendazole and azithromycin, including both data on pharmacokinetic interactions and data from previous experimental and observational studies conducted in NTD-endemic populations. We searched PubMed, Google Scholar, research and conference abstracts, gray literature, and national policy documents. We limited the publication language to English and used a search period from January 1st, 1995 through October 1st, 2022. Search terms were: azithromycin and ivermectin and albendazole, mass drug administration co-administration trials, integrated mass drug administration, mass drug administration safety, pharmacokinetic dynamics, and azithromycin and ivermectin and albendazole. We excluded papers if they did not include data on co-administration of azithromycin and both albendazole and ivermectin, or azithromycin with either albendazole or ivermectin alone.. We identified a total of 58 potentially relevant studies. Of these we identified 7 studies relevant to the research question and which met our inclusion criteria. Three papers analyzed pharmacokinetic and pharmacodynamic interactions. No study found evidence of clinically significant drug-drug interactions likely to impact safety or efficacy. Two papers and a conference presentation reported data on the safety of combinations of at least two of the drugs. A field study in Mali suggested the rates of adverse events were similar with combined or separate administration, but was underpowered. A further field study in Papua New Guinea used all three drugs as part of a four-drug regimen also including diethylcarbamazine; in this setting, co-administration appeared safe but there were issues with the consistency in how adverse events were recorded.. There are relatively limited data on the safety profile of co-administering ivermectin, albendazole and azithromycin as an integrated regimen for NTDs. Despite the limited amount of data, available evidence suggests that such a strategy is safe with an absence of clinically important drug-drug interactions, no serious adverse events reported and little evidence for an increase in mild adverse events. Integrated MDA may be a viable strategy for national NTD programmes.

Topics: Albendazole; Azithromycin; Drug Therapy, Combination; Elephantiasis, Filarial; Feasibility Studies; Humans; Ivermectin; Mass Drug Administration; Neglected Diseases

Neglected tropical diseases are co-endemic in many areas of the world, including sub Saharan Africa. Currently lymphatic filariasis (albendazole/ivermectin) and trachoma (azithromycin) are treated separately. Consequently, financial and logistical benefit can be gained from integration of preventive chemotherapy programs in such areas.. 4 villages in two co-endemic districts (Kolondièba and Bougouni) of Sikasso, Mali, were randomly assigned to coadministered treatment (ivermectin/albendazole/azithromycin) or standard therapy (ivermectin/albendazole with azithromycin 1 week later). These villages had previously undergone 4 annual MDA campaigns with ivermectin/albendazole and 2 with azithromycin. One village was randomly assigned to each treatment arm in each district. There were 7515 eligible individuals in the 4 villages, 3011(40.1%) of whom participated in the study. No serious adverse events occurred, and the majority of adverse events were mild in intensity (mainly headache, abdominal pain, diarrhoea and "other signs/symptoms"). The median time to the onset of the first event, of any type, was later (8 days) in the two standard treatment villages than in the co-administration villages. Overall the number of subjects reporting any event was similar in the co-administration group compared to the standard treatment group [18.7% (281/1501) vs. 15.8% (239/1510)]. However, the event frequency was higher in the coadministration group (30.4%) than in the standard treatment group (11.0%) in Kolondièba, while the opposite was observed in Bougouni (7.1% and 20.9% respectively). Additionally, the overall frequency of adverse events in the co-administration group (18.7%) was comparable to or lower than published frequencies for ivermectin+albendazole alone.. These data suggest that co-administration of ivermectin+albendazole and azithromycin is safe; however the small number of villages studied and the large differences between them resulted in an inability to calculate a meaningful overall estimate of the difference in adverse event rates between the regimens. Further work is therefore needed before co-administration can be definitively recommended.. ClinicalTrials.gov; NCT01586169.

Topics: Adolescent; Adult; Aged; Albendazole; Anthelmintics; Anti-Bacterial Agents; Azithromycin; Chemoprevention; Child; Child, Preschool; Coinfection; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Elephantiasis, Filarial; Female; Humans; Ivermectin; Male; Mali; Middle Aged; Neglected Diseases; Trachoma; Young Adult

Trachoma is the world's most frequent cause of blindness from an infectious agent. The disease caused by infection is associated with lack of access to sanitation and low hygiene standards. Trachoma is controlled through the Surgery, Antibiotics, Facial cleanliness, and Environmental improvement (SAFE) strategy, which delivers azithromycin (AZM) mass drug administration (MDA) in endemic areas. The putative vector Musca sorbens principally reproduce in human faecal matter left in the environment due to open defecation. Ivermectin (IVM) is on the WHO's essential medicines list and is administered as preventative chemotherapy against two neglected tropical diseases (NTDs)-onchocerciasis, as an annual or bi-annual treatment, and lymphatic filariasis, as an annual treatment in combination with albendazole. Ivermectin has a known inhibitive effect on insects that reproduce in dung. To assess if IVM could be a viable vector control tool against M. sorbens, this study evaluates existing data from trachoma, onchocerciasis and lymphatic filariasis mass drug administration (MDA) operations in Ethiopia. Persistent and recrudescent trachoma in evaluation units (EUs) were examined for whether AZM MDA in EUs was accompanied by IVM MDA, and whether co-administration was associated with greater likelihood of trachoma control. Results show an association suggesting that EUs that received both IVM and AZM MDA benefit from improved control of trachoma in persistent or recrudescent areas, when compared to EUs that received AZM MDA. This initial investigation supports the potential for ivermectin's use to support SAFE. Findings warrant further work to validate ivermectin's impact on M. sorbens reproduction through controlled lab and field-based studies.

Topics: Animals; Anti-Bacterial Agents; Azithromycin; Chlamydia trachomatis; Elephantiasis, Filarial; Humans; Ivermectin; Muscidae; Onchocerciasis; Trachoma