Treatment of tungiasis using a tea tree oil-based gel formulation: protocol for a randomised controlled proof-of-principle trial.

INTRODUCTION: Tungiasis (sand flea disease or jigger infestation) is a neglected tropical disease caused by penetration of female sand fleas, Tunga penetrans, in the skin. The disease inflicts immense pain and suffering on millions of people, particularly children, in Latin America, the Caribbean and sub-Saharan Africa. Currently, there is no standard treatment for tungiasis, and a simple, safe and effective tungiasis treatment option is required. Tea tree oil (TTO) has long been used as a parasiticidal agent against ectoparasites such as headlice, mites and fleas with proven safety and efficacy data. However, current data are insufficient to warrant a recommendation for its use in tungiasis. This trial aims to generate these data by comparing the safety and efficacy of a 5% (v/w) TTO proprietary gel formulation with 0.05% (w/v) potassium permanganate (KMnO4) solution for tungiasis treatment. METHODS AND ANALYSIS: This trial is a randomised controlled trial (RCT) in primary schools (n=8) in South-Western Kenya. The study will include school children (n=88) aged 6-15 years with a confirmed diagnosis of tungiasis. The participants will be randomised in a 1:1 ratio to receive a 3-day two times a day treatment of either 5% TTO gel or 0.05% KMnO4 solution. Two viable embedded sandflea lesions per participant will be targeted and the viability of these lesions will be followed throughout the study using a digital handheld microscope. The primary outcome is the proportion of observed viable embedded sand fleas that have lost viability (non-viable lesions) by day 10 (9 days after first treatment). Secondary outcomes include improvement in acute tungiasis morbidities assessed using a validated severity score for tungiasis, safety assessed through adverse events and product acceptability assessed by interviewing the participants to rate the treatment in terms of effectiveness, side effects, convenience, suitability and overall satisfaction. ETHICS AND DISSEMINATION: The trial protocol has been reviewed and approved by the University of Canberra Human Research Ethics Committee (HREC-2019-2114). The findings of the study will be presented at scientific conferences and published in a peer-reviewed journal. TRIAL REGISTRATION NUMBERS: Australian New Zealand Clinical Trials Registry (ACTRN12619001610123); PACTR202003651095100 and U1111-1243-2294.

Efficacy of a mixture of neem seed oil (Azadirachta indica) and coconut oil (Cocos nucifera) for topical treatment of tungiasis. A randomized controlled, proof-of-principle study.

BACKGROUND: Tungiasis 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. METHODOLOGY: Ninety-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. RESULTS: The 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. CONCLUSIONS: Whilst 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 REGISTRATION: The 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).

Prevention of tungiasis and tungiasis-associated morbidity using the plant-based repellent Zanzarin: a randomized, controlled field study in rural Madagascar.

BACKGROUND: Tungiasis, a parasitic skin disease caused by the female sand flea Tunga penetrans, is a prevalent condition in impoverished communities in the tropics. In this setting, the ectoparasitosis is associated with important morbidity. It causes disfigurement and mutilation of the feet. Feasible and effective treatment is not available. So far prevention is the only means to control tungiasis-associated morbidity. METHODOLOGY: In two villages in Central Madagascar, we assessed the efficacy of the availability of closed shoes and the twice-daily application of a plant-based repellent active against sand fleas (Zanzarin) in comparison to a control group without intervention. The study population was randomized into three groups: shoe group, repellent group and control group and monitored for ten weeks. The intensity of infestation, the attack rate and the severity of tungiasis-associated morbidity were assessed every two weeks. FINDINGS: In the repellent group, the median attack rate became zero already after two weeks. The intensity of the infestation decreased constantly during the observation period and tungiasis-associated morbidity was lowered to an insignificant level. In the shoe group, only a marginal decrease in the intensity of infestation and in the attack rate was observed. At week 10, the intensity of infestation, the attack rate and the severity score for acute tungiasis remained significantly higher in the shoe group than in the repellent group. Per protocol analysis showed that the protective effect of shoes was closely related to the regularity with which shoes were worn. CONCLUSIONS: Although shoes were requested by the villagers and wearing shoes was encouraged by the investigators at the beginning of the study, the availability of shoes only marginally influenced the attack rate of female sand fleas. The twice-daily application of a plant-based repellent active against sand fleas reduced the attack to zero and lowered tungiasis-associated morbidity to an insignificant level.

Control of tungiasis through intermittent application of a plant-based repellent: an intervention study in a resource-poor community in Brazil.

BACKGROUND: Tungiasis, an ectoparasitosis caused by the female sand flea Tunga penetrans, is an important health problem in many impoverished communities in the tropics. Sand flea disease is associated with a broad spectrum of clinical pathology and severe sequels are frequent. Treatment options are limited. METHODOLOGY/PRINCIPAL FINDINGS: We assessed the effectiveness of the intermittent application of the plant-based repellent Zanzarin to reduce infestation intensity and tungiasis-associated morbidity in a resource-poor community in Brazil, characterized by a very high attack rate. The study population was randomized into three cohorts. Initially, during a period of four weeks, the repellent was applied twice daily to the feet of all cohort members. This reduced the number of embedded sandfleas to 0 in 98% of the participants. Thereafter members of cohort A applied the repellent every second week twice daily for one week, members of cohort B every fourth week for one week, and members of cohort C served as controls. Infestation intensity and tungiasis-associated morbidity were monitored during five months. The intermittent application of Zanzarin for one week every second week significantly reduced infestation intensity from a median 4 lesions (IQR 1-9) during the whole transmission season. In contrast, in cohort B (application of the repellent every fourth week) the infestation intensity remained twice as high (median 8 lesions, IQR 9-16; p = 0.0035), and in the control cohort C 3.5 times as high (median 14 lesions; IQR 7-26; p = 0.004 during the transmission season). Tungiasis-related acute pathology remained very low in cohort A (median severity score 2; IQR 1-4) as compared to cohort B (median severity score 5; IQR 3-7; p<0.001), and control cohort C (median severity score 6.5; IQR 4-8; p<0.001). CONCLUSIONS/SIGNIFICANCE: Our study shows that in a setting with intense transmission, tungiasis-associated morbidity can be minimized through the intermittent application of a plant-based repellent.

Epidemiological and clinical characteristics of hookworm-related cutaneous larva migrans.

Hookworm-related cutaneous larva migrans is caused by the migration of animal hookworm larvae in the human skin. The disease mainly occurs in resource-poor communities in the developing world, but it is also reported sporadically in high-income countries and in tourists who have visited the tropics. Diagnosis is made clinically in the presence of a linear serpiginous track moving forward in the skin, associated with itching and a history of exposure. Itching is typically very intense and can prevent patients from sleeping. Bacterial superinfection occurs as a result of scratching. Treatment is based on oral drugs (albendazole or ivermectin) or the topical application of tiabendazole. To control hookworm-related cutaneous larva migrans at the community level, regular treatment of dogs and cats with anthelmintic drugs is necessary, but this is seldom feasible in resource-poor settings. Animals should be banned from beaches and playgrounds. For protection at the individual level, unprotected skin should not come into contact with possibly contaminated soil.

A plant-based repellent protects against Tunga penetrans infestation and sand flea disease.

Tungiasis is a parasitic skin disease prevalent in impoverished populations in the tropics and associated with considerable morbidity. Treatment options are limited and prophylaxis has never been attempted. We assessed the effectiveness of a plant-based repellent to prevent infestation with Tunga penetrans and sand flea disease in an urban squatter settlement in Fortaleza, Northeast Brazil. Two cohorts were formed. One cohort started with the intervention while another served as control. The plant-based repellent Zanzarin was applied twice daily on the skin of the feet. After 4 weeks and a wash-out-phase of another 2 weeks, cross-over was performed. Study members were examined twice per week for the presence of newly embedded sand fleas. The number of viable and dead sand fleas and the total number of sand flea lesions were determined. Sentinel rats were used to assess local transmission dynamics. Outcome measures were the number of newly embedded sand fleas per individual per day, number of sand flea lesions per individual according to the stage, as well as type and degree of clinical pathology. Zanzarin applied twice daily on the feet reduced the number of newly embedded fleas by 92% (interquartile range 81-100%), the total number of lesions by 87% (81-98%) and reversed tungiasis-associated clinical pathology almost completely. In conclusion, in a setting in which tungiasis is an important health threat, the daily application of a plant-based repellent prevented the infestation with T. penetrans and sand flea disease.

Scabies.

Scabies is a neglected parasitic disease that is a major public health problem in many resource-poor regions. It causes substantial morbidity from secondary infections and post-infective complications such as acute post-streptococcal glomerulonephritis. Disease control requires treatment of the affected individual and all people they have been in contact with, but is often hampered by inappropriate or delayed diagnosis, poor treatment compliance, and improper use of topical compounds such as permethrin, lindane, or benzyl benzoate. In addition to concerns over toxicity with such compounds, parasite resistance seems to be increasing. Oral ivermectin is an alternative that has been used successfully in community control programmes. Plant derivatives such as turmeric, neem, and tea tree oil are also promising future treatments. The disease is strongly associated with poverty and overcrowding, and the associated stigma can ostracise affected individuals. Treatment of scabies in poor countries needs to integrate drug treatment programmes with efforts to improve the socioeconomic conditions and education programmes to reduce stigma. We expect the future to bring more sensitive and specific clinical and laboratory-based diagnostic methods, as well as new therapeutic strategies.