Efficacy of monthly treatment with oral fluralaner (Bravecto® 1-Month) against Tunga penetrans in dogs in Brazil: a randomized, double-blind, controlled field study.

BACKGROUND: Tungiasis is a neglected tropical disease caused by the adult female sand flea (Tunga penetrans). Dogs are considered important reservoirs of T. penetrans in Brazil. The aim of this study was to determine the monthly insecticidal efficacy of a single oral administration of fluralaner at a dose of 10-18 mg/kg (Bravecto® 1-Month, also registered as Defenza® in some countries; MSD Animal Health) in dogs naturally infested with T. penetrans. METHODS: This clinical trial was conducted in a rural community located in Ilhéus, Bahia, Brazil. A total of 64 dogs were selected and distributed in a completely randomized design between a treated group (TG) that received one single dose of Bravecto® 1-Month (Defenza®) and a negative control group (CG) that received no treatment. Each group was composed of 32 dogs. The evaluations took place on days 0, 7 ± 2, 14 ± 2, 21 ± 2, 28 ± 2, 35 ± 2, and 42 ± 2 post treatment, in which the dogs were inspected to evaluate the infestation stage and classify lesions associated with tungiasis. The primary efficacy was determined from the percentage of treated dogs free of fleas (stage II and III lesions) after administration of the formulation at each evaluation time. Secondary efficacy was based on the number of active lesions (stages II and III) in each group at each evaluation time. The clinical condition of the animals was defined based on the Severity Score for Acute Dog Tungiasis (SCADT), which is related to the number and severity of lesions. RESULTS: The primary efficacy of the product was greater than 95.0% from days 7 to 21 and reached 100.0% between days 28 and 42, with a significant association between treatment and infestation decline (P < 0.025) between days 7 and 42. Secondary drug efficacy was greater than 99.9% from days 7 to 21, reaching 100.0% between days 28 and 42 (P < 0.05). The treated dogs also scored lower on the SCADT than the control animals did during the entire clinical evaluation period (P < 0.05). CONCLUSIONS: A single administration of Bravecto® 1-Month (Defenza®) was effective in eliminating Tunga penetrans infestations, as well as in preventing parasitism for at least 42 days after treatment.

Therapeutic Potential of Tea Tree Oil for Tungiasis.

Tungiasis (sand flea disease) is a neglected tropical disease caused by penetration of female sand fleas, Tunga penetrans, into a person's skin usually in their feet. The disease inflicts immense pain and suffering on millions of people, particularly children. The condition is most prevalent in Latin America, the Caribbean, and sub-Saharan Africa. Currently, there is no standard drug treatment for tungiasis. The available treatment options are fairly limited and unrealistic to use in endemic areas; as a result, in desperation, the affected people do more harm to themselves by extracting the fleas with non-sterile instruments, further exposing themselves to secondary bacterial infections and/or transmission of diseases such as hepatitis B virus, hepatitis C virus, or HIV. This highlights the urgent need for simpler, safer, and effective treatment options for tungiasis. Tea tree oil (TTO) has long been used as an antiseptic with extensive safety and efficacy data. The evidence on parasiticidal properties of TTO against ectoparasites such as head lice, mites, and fleas is also compelling. The purpose of this review is to discuss the current tungiasis treatment challenges in endemic settings and highlight the potential role of TTO in the treatment of tungiasis.

The efficacy of topical, oral and surgical interventions for the treatment of tungiasis: A systematic review of the literature.

BACKGROUND: Tungiasis is a neglected disease caused by Tunga penetrans that can be complicated by secondary infections and local tissue destruction. Adequate treatment is important, especially in vulnerable populations; potential treatment options proposed range from surgical extraction to the use of oral and topical medications. We aimed to perform a systematic review to assess the efficacy of topical, oral and surgical interventions for the treatment of tungiasis. METHODOLOGY/PRINCIPAL FINDINGS: The present review is registered in PROSPERO (CRD42021234741). On September 1, 2020, we searched PubMed, EMBASE, Scopus, Web of Science, Science Direct, Scielo and LILACS BVS. We included clinical trials and longitudinal observational studies that evaluated any topical, systemic or mechanical treatment for tungiasis. We used the Revised Cochrane Risk of Bias (RoB) Tool for Randomized Trials for clinical trial analysis. Qualitative and quantitative descriptive syntheses were performed. Our search strategy resulted in 3376 references. Subsequently, 2568 titles/abstracts and 114 full texts were screened. We finally included 19 articles; 9 were classified as clinical trials. Two and 3 articles presented low and some RoB, respectively, according to the tool. Only two articles tested the efficacy of oral medications (niridazole, ivermectin), with discouraging results. Six clinical trials evaluated topical products for the treatment of tungiasis; 2 evaluated dimeticone-based compounds and reported positive results in lesion reduction and cure. None reported significant adverse reactions. Surgical extraction was evaluated only in observational studies. CONCLUSIONS/SIGNIFICANCE: We conclude that, although surgical extraction is the most commonly used treatment, there is sufficient evidence supporting the use of occlusive agents, especially manufactured dimeticone-based products.

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).

Tungiasis-related life quality impairment in children living in rural Kenya.

BACKGROUND: Tungiasis (sand flea disease) is a neglected tropical skin disease caused by female sand fleas (Tunga spp.) embedded in the skin of the host. The disease is common in sub-Saharan Africa and predominantly affects children living in impoverished rural communities. In these settings tungiasis is associated with important morbidity. Whether tungiasis impairs life quality has never been studied. METHODS: The study was performed in 50 children with tungiasis, living in resource-poor communities in coastal Kenya. Based on the Dermatology Life Quality Index (DLQI) a tool was developed to determine life quality impairment associated with tungiasis in children, the tungiasis-related Dermatology of Life Quality Index (tungiasis-related-DLQI). Pain and itching were assessed using visual scales ranging from 0-3 points. The intensity of infection and the acute and chronic severity of tungiasis were determined using standard methods. RESULTS: Seventy eight percent of the patients reported a moderate to very large effect of tungiasis on life quality at the time of the diagnosis. The degree of impairment correlated with the number of viable sand fleas present in the skin (rho = 0.64, p < 0.001), the severity score of acute clinical pathology (rho = 0.74, p < 0.001), and the intensity of pain (rho = 0.82, p < 0.001). Disturbance of sleep and concentration difficulties were the most frequent restriction categories (86% and 84%, respectively). Four weeks after curative treatment, life quality had improved significantly. On the individual level the amelioration of life quality correlated closely with the regression of clinical pathology (rho = 0.61, p < 0.001). CONCLUSION: The parasitic skin disease tungiasis considerably impairs life quality in children in rural Kenya. After effective treatment, life quality improves rapidly.

High intensity of Tunga penetrans infection causing severe disease among pigs in Busoga, South Eastern Uganda.

BACKGROUND: Towards the improvement of stakeholders' awareness of animal tungiasis, we report 10 unusual severe clinical cases of pig tungiasis which were associated with very high infection intensities of T. penetrans in an endemic area. RESULTS: Morbidity of ten pigs with high sand flea intensities detected during high transmission seasons in an endemic area in Busoga sub region, Uganda is described in detail. The cases of pigs presented with a very high number of embedded sand fleas (median = 276, range = 141-838). Acute manifestations due to severe tungiasis included ulcerations (n = 10), abscess formation (n = 6) and lameness (n = 9). Chronic morphopathological presentations were overgrowth of claws (n = 5), lateral deviation of dew claws (n = 6), detachment (n = 5) or loss of dew claws (n = 1). Treatment of severe cases with a topical insecticidal aerosol containing chlorfenvinphos, dichlorvos and gentian violet resolved acute morbidity and facilitated healing by re-epithelialisation. CONCLUSIONS: The presentations of tungiasis highlighted in this report show that high intensities of embedded T. penetrans can cause a severe clinical disease in pigs. Effective tungiasis preventive measures and early diagnosis for treatment could be crucial to minimize its effects on animal health.

Disseminated tungiasis in a 78-year-old woman from Tanzania: a case report.

BACKGROUND: Tungiasis is one of the neglected tropical diseases; it affects up to 40% of individuals living in societies with poor housing and sanitation standards. In endemic areas, Tunga infestation, which predominantly affects the periungual areas of the lower limbs in humans, is associated with considerable morbidity and poor quality of life. CASE PRESENTATION: A 78-year-old woman of African descent presented with pain, inflammation, suppuration, ulceration, and deformation of digits of all four limbs. She had a total of 1146 embedded sand fleas: 812 in lower limbs and 334 in her hands. She was febrile; her full blood count revealed pancytopenia and blood cultures were positive for Staphylococcus aureus and Streptococcus pyogenes isolates. Furthermore, she had severe hyponatremia. We applied 20% salicylated petroleum jelly followed by the manual removal of embedded sand fleas with a sterile needle. Intravenously administered piperacillin-tazobactam, topical ivermectin, ferrous sulfate, folic acid, tolvaptan, albendazole, multivitamins, and tetanus prophylaxis were instituted. She was discharged home after 16 days of hospitalization. CONCLUSIONS: Tungiasis is a neglected disease of concern in underprivileged societies that is preventable and curable. Early recognition and prompt treatment is crucial to prevent complications in this disease which may potentially mimic other conditions resulting in erroneous management.

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

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.

Treatment of Tungiasis with dimeticone: a proof-of-principle study in rural Kenya.

Tungiasis (sand flea disease) is a neglected tropical disease, prevalent in resource-poor communities in South America and sub-Saharan Africa. It is caused by an inflammatory response against penetrated female sand fleas (Tunga penetrans) embedded in the skin of the host. Although associated with debilitating acute and chronic morbidity, there is no proven effective drug treatment. By consequence patients attempt to remove embedded sand fleas with non-sterile sharp instruments, such as safety pins, a procedure that represents a health threat by itself. In this proof-of-principle study we compared the topical application of a mixture of two dimeticones of low viscosity (NYDA) to the topical application of a 0.05% solution of KMnO4 in 47 school children in an endemic area in rural Kenya. The efficacy of the treatment was assessed during a follow up period of seven days using viability signs of the embedded parasites, alterations in the natural development of lesion morphology and the degree of local inflammation as outcome measures. Seven days after treatment, in the dimeticone group 78% (95% CI 67-86%) of the parasites had lost all signs of viability as compared to 39% (95% CI 28-52%) in the KMnO4 group (p<0.001). In the dimeticone group 90% (95% CI 80-95%) of the penetrated sand fleas showed an abnormal development already after 5 days, compared to 53% (95% CI 40-66%; p<0.001) in the KMnO4 group. Seven days after treatment, signs of local skin inflammation had significantly decreased in the dimeticone group (p<0.001). This study identified the topical application of dimeticones of low viscosity (NYDA) as an effective means to kill embedded sand fleas. In view of the efficacy and safety of the topical treatment with dimeticone, the mechanical extraction of embedded sand fleas using hazardous instruments is no longer warranted.

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.

Regression of severe tungiasis-associated morbidity after prevention of re-infestation: a case series from rural Madagascar.

Tungiasis (sand flea disease) is a neglected tropical disease. Heavy infestation results in mutilation of the feet and difficulty in walking. We identified eight individuals with extremely severe tungiasis in rural Madagascar. To prevent reinfestation, four individuals received solid shoes and four received a daily application of an herbal repellent effective against Tunga penetrans. Over a period of 10 weeks the feet were examined and the severity of tungiasis-associated morbidity was measured. Within this period, the severity score for acute tungiasis decreased 41% in the shoe group and 89% in the repellent group. The four major inflammation-related symptoms disappeared in the four patients of the repellent group, but only in two patients of the shoe group. Those observations indicate that cases with extremely severe tungiasis, associated morbidity almost totally disappears within 10 weeks if the feet are protected by a repellent. Wearing shoes reduced acute morbidity only marginally.

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.