Dataset Information

Successful Treatment of Severe Tungiasis in Pigs Using a Topical Aerosol Containing Chlorfenvinphos, Dichlorphos and Gentian Violet.

ABSTRACT:

Background

In endemic communities, zoonotic tungiasis, a severe skin disease caused by penetrating female sand fleas, is a public health hazard causing significant human and animal morbidity. No validated drugs are currently available for treatment of animal tungiasis. Due to the reservoir in domestic animals, integrated management of human and animal tungiasis is required to avert its negative effects.

Methods and principal findings

A topical aerosol containing chlorfenvinphos 4.8%, dichlorphos 0.75% and gentian violet 0.145% licensed to treat tick infestations, myiasis and wound sepsis in animals in the study area, was tested for its potential tungicidal effects in a randomized controlled field trial against pig tungiasis in rural Uganda. Animals with at least one embedded flea were randomized in a treatment (n = 29) and a control (n = 26) group. One week after treatment, 58.6% of the treated pigs did not show any viable flea lesion whereas all control pigs had at least one viable lesion. After treatment the number of viable lesions (treated median = 0, overall range = 0-18 vs. control median = 11.5, range = 1-180) and the severity score for estimating acute pathology in pig tungiasis (treated median = 1, range = 0-3.5 vs. control median = 7, range = 0-25) were significantly lower in treated than in control pigs (p < 0.001). In the treatment group the median number of viable flea lesions decreased from 8.5 to 0 (p < 0.001). Similarly, the median acute severity score dropped from 6 to 1 (p < 0.001). Every pig in the treatment group showed a decrease in the number of viable fleas and tungiasis-associated acute morbidity while medians for both increased in the control group.

Conclusions

The study demonstrates that a topical treatment based on chlorfenvinphos, dichlorphos and gentian violet is highly effective against pig tungiasis. Due to its simplicity, the new approach can be used for the treatment of individual animals as well as in mass campaigns.

SUBMITTER: Mutebi F

PROVIDER: S-EPMC5058476 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Publications

Successful Treatment of Severe Tungiasis in Pigs Using a Topical Aerosol Containing Chlorfenvinphos, Dichlorphos and Gentian Violet.

Mutebi Francis F von Samson-Himmelstjerna Georg G Feldmeier Hermann H Waiswa Charles C Bukeka Muhindo Jeanne J Krücken Jürgen J

PLoS neglected tropical diseases 20161011 10

<h4>Background</h4>In endemic communities, zoonotic tungiasis, a severe skin disease caused by penetrating female sand fleas, is a public health hazard causing significant human and animal morbidity. No validated drugs are currently available for treatment of animal tungiasis. Due to the reservoir in domestic animals, integrated management of human and animal tungiasis is required to avert its negative effects.<h4>Methods and principal findings</h4>A topical aerosol containing chlorfenvinphos 4. ...[more]

PMID: 27727268

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Project description:ImportanceTriggering the extrinsic apoptotic pathway is an effective way to kill cutaneous T-cell lymphoma (CTCL) cells in vitro and ex vivo.ObjectiveTo compare small molecules that induce extrinsic apoptosis in CTCL to identify and analyze compounds that induce high levels of tumor cell death and block tumor cell growth.Design, setting, and participantsFrom November 5, 2014, to January 30, 2018, this study performed high-throughput small molecule screening of 1710 compounds followed by detailed analysis of the ability of gentian violet (GV) to promote apoptosis and inhibit proliferation of CTCL cells.ExposuresIn vitro and ex vivo analyses using enzyme-linked immunosorbent assays, flow cytometry, and immunoblotting.Main outcomes and measuresApoptosis, cleaved caspases, extrinsic apoptotic death receptors and ligands, cell proliferation, nuclear factor-?B expression, and other factors.ResultsThis study used high-throughput screening to detect cleaved caspase 8 induced in CTCL cells by 1710 unique compounds. The nonprescription, topical antimicrobial remedy GV induced more total apoptosis than did nitrogen mustard (mechlorethamine). Furthermore, GV induced 4 to 6 times greater apoptosis in CTCL lines than in normal keratinocytes, suggesting a favorable topical toxicity profile. In addition to increasing caspase 8, GV also upregulated death receptors 4 and 5, tumor necrosis factor (TNF)-related apoptosis-inducing ligand, and Fas ligand but not the Fas receptor, TNF receptor, or TNF-? ligand. These results are consistent with induction of extrinsic apoptosis via the Fas and TNF-related apoptosis-inducing ligand pathways. Increased phosphorylation of phospholipase C-?1, Ca2+ influx, and reactive oxygen species were also detected, indicating that the mechanism of Fas ligand upregulation involves key elements of the activation-induced cell death pathway. In ex vivo studies, 1-?mol/L GV induced up to 90% CTCL apoptosis in Sézary blood cells. In addition, GV reduced expression of antiapoptotic myeloid cell leukemia 1 and proproliferative nuclear factor-?B components and increased inhibitory ?B levels. This finding was associated with cell cycle arrest and reduced CTCL tumor cell proliferation. Furthermore, the CTCL killing associated with GV was augmented when used in combination with methotrexate.Conclusions and relevanceThis study found that GV attacked tumor viability and growth in CTCL. Although purple at neutral pH, GV can be rendered colorless by altering its pH. These preclinical findings may help to broaden knowledge of the antineoplastic features of GV and provide a rationale for clinical studies of its use as a novel, inexpensive, topical therapy for CTCL that is available worldwide.

Project description:BackgroundTungiasis is a neglected tropical skin disease caused by the female sand flea (Tunga penetrans), which burrows into the skin causing intense pain, itching and debilitation. People in endemic countries do not have access to an effective and safe home treatment. The aim of this study was to determine the efficacy of a traditionally used and readily available mixture of neem and coconut oil for treatment of tungiasis in coastal Kenya.MethodologyNinety-six children aged 6-14 years with at least one embedded viable flea were randomized to be treated with either a mixture of 20% neem (Azadirachta indica) seed oil in coconut oil (NC), or with a 0.05% potassium permanganate (KMnO4) foot bath. Up to two viable fleas were selected for each participant and monitored for 6 days after first treatment using a digital microscope for signs of viability and abnormal development. Acute pathology was assessed on all areas of the feet using a previously established score. Children reported pain levels and itching on a visual scale.ResultsThe NC was not more effective in killing embedded sand fleas within 7 days than the current standard with KMnO4, killing on average 40% of the embedded sand fleas six days after the initial treatment. However, the NC was superior with respect to the secondary outcomes of abnormal development and reduced pathology. There was a higher odds that fleas rapidly aged in response to NC compared to KMnO4 (OR 3.4, 95% CI: 1.22-9.49, p = 0.019). NC also reduced acute pathology (p<0.005), and there was a higher odds of children being pain free (OR 3.5, p = 0.001) when treated with NC.ConclusionsWhilst NC did not kill more fleas than KMnO4 within 7 days, secondary outcomes were better and suggest that a higher impact might have been observed at a longer observation period. Further trials are warranted to assess optimal mixtures and dosages.Trial registrationThe study was approved by the Kenya Medical Research Institute (KEMRI) Scientific and Ethical Review Unit (SERU), Nairobi (Non-SSC Protocol No. 514, 1st April 2016) and approved by and registered with the Pharmacy and Poisons Board's Expert Committee on Clinical Trials PPB/ECCT/16/05/03/2016(94), the authority mandated, by Cap 244 Laws of Kenya, to regulate clinical trials in the country. The trial was also registered with the Pan African Clinical Trial Registry (PACTR201901905832601).

Dataset Information

Successful Treatment of Severe Tungiasis in Pigs Using a Topical Aerosol Containing Chlorfenvinphos, Dichlorphos and Gentian Violet.

Background

Methods and principal findings

Conclusions

Publications

Successful Treatment of Severe Tungiasis in Pigs Using a Topical Aerosol Containing Chlorfenvinphos, Dichlorphos and Gentian Violet.

Similar Datasets

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