Alterations of plasma circulating microRNAs in BALB/c mice with Toxocara canis visceral and cerebral larva migrans.

BACKGROUND: Human toxocariasis is a neglected parasitic disease characterised by the syndromes visceral, cerebral, and ocular larva migrans. This disease is caused by the migrating larvae of Toxocara roundworms from dogs and cats, affecting 1.4 billion people globally. Via extracellular vesicles (EVs), microRNAs have been demonstrated to play roles in host-parasite interactions and proposed as circulating biomarkers for the diagnosis and follow-up of parasitic diseases. METHODS: Small RNA-seq was conducted to identify miRNAs in the infective larvae of T. canis and plasma EV-containing preparations of infected BALB/c mice. Differential expression analysis and target prediction were performed to indicate miRNAs involved in host-parasite interactions and miRNAs associated with visceral and/or cerebral larva migrans in the infected mice. Quantitative real-time polymerase chain reaction (PCR) was used to amplify circulating miRNAs from the infected mice. RESULTS: This study reports host and parasite miRNAs in the plasma of BALB/c mice with visceral and cerebral larva migrans and demonstrates the alterations of these miRNAs during the migration of larvae from the livers through the lungs and to the brains of infected mice. After filtering unspecific changes in an irrelevant control, T. canis-derived miRNAs and T. canis infection-induced differential miRNAs are predicted to modulate genes consistently involved in mitogen-activated protein kinase (MAPK) signalling and pathways regulating axon guidance and pluripotency of stem in the infected mice with visceral and cerebral larva migrans. For these plasma circulating miRNAs predicted to be involved in host-parasite crosstalk, two murine miRNAs (miR-26b-5p and miR-122-5p) are experimentally verified to be responsive to larva migrans and represent circulating biomarker candidates for visceral and cerebral toxocariasis in BALB/c mice. CONCLUSIONS: Our findings provide novel insights into the crosstalk of T. canis and the mammalian host via plasma circulating miRNAs, and prime agents and indicators for visceral and cerebral larva migrans. A deep understanding of these aspects will underpin the diagnosis and control of toxocariasis in humans and animals.

Ecoepidemiology of Ancylostoma spp. in Urban-Marginal and Rural Sectors of the Ecuadorian Coast and Prevalence of Cutaneous Larvae Migrans.

BACKGROUND Ancylostoma spp., including A. duodenale, A. braziliense, A. caninum, and A. ceylanicum, are hookworms that are transmitted from infected soil and by contact with domestic animals and rodent hosts, and can cause systemic disease and cutaneous larva migrans. The objective of this study was to describe the ecoepidemiology of Ancylostoma caninum and Ancylostoma spp. in urban-marginal sectors and in rural sectors located in Ecuador. MATERIAL AND METHODS Through addressed sampling, a total of 498 domestic dogs and 40 synanthropic rodents were analyzed via the following coproparasitic methods: direct, flotation, sedimentation with centrifugation using saline (egg identification), modified Baermann (larval identification), and morphometric methods (confirmation). A total of 236 people were surveyed, and a clinical analysis was performed via physical examination. The environmental variables were obtained through reports from the INAMHI of Ecuador and the use of online environmental programs. Through surveys, data related to social determinants were obtained. Epidemiological indicators (prevalence, morbidity, and mortality) were obtained through microbial analysis and surveys. RESULTS A total of 250 domestic dogs were diagnosed with Ancylostoma caninum (50, 20%), and 41 were diagnosed with Ancylostoma spp. (8.23%). One synanthropic rodent (2.5%) was positive for A. caninum. In the clinical analysis, 3 patients were identified as positive (1.27%) for cutaneous larva migrans (CLM). Likewise, environmental variables and social determinants influence the transmission, prevalence, and nature of parasitism by hookworm. CONCLUSIONS People, domestic dogs, and rodents were infected with these parasites. Consequently, there is a risk of ancylostomiasis and cutaneous larvae migrans spreading.

Occupational risk of cutaneous larva migrans: A case report and a systematic literature review.

Cutaneous larva migrans (CLM) is a parasitic zoonosis of warm tropical and subtropical areas, although autochthonous cases have been increasingly reported in Western European countries. Data on the prevalence of CLM as an occupational disease in workers exposed to potentially contaminated soil or in close contact with dogs and cats are scant. Herein, we report an autochthonous case of CLM in a dog breeder from southern Italy (Apulia region), along with a systematic literature review describing the risk of CLM infection, mainly according to job categories. The patient was referred to the dermatology unit presenting a serpiginous lesion on his hand, raising the suspected CLM diagnosis. In non-endemic areas, CLM might represent a challenge for physicians in terms of diagnosis, treatment, and prevention, particularly in workplaces. The multidisciplinary approach in the diagnosis of CLM with the involvement of different scientific competences (i.e., dermatologists, veterinarians, and occupational physicians) may contribute to further assess the distribution of human CLM and associated risk factors, toward reducing the risk for the infection.

Toxocariasis and the clinical spectrum.

Toxocara canis and T. cati are among the most widely distributed helminthic species in the world with a high zoonotic impact. Millions of people are infecteda and hundreds of thousands are suffering from toxocarosis, a disease encompassing four different entities: larva migrans visceralis (VLM) syndrome, ocular larva migrans (OLM) syndrome, covert toxocarosis (covT), common toxocarosis (comT) and neurotoxocarosis (NT). Toxocara infections in humans may remain clinically inapparent but may also induce severe diseases. This contribution gives a synoptic overview of the most important historical, clinical, diagnostic and therapeutical aspects of toxocarosis in humans.

History of Toxocara and the associated larva migrans.

This review covers the systematics and nomenclature of the Ascaridoid genus toxocara, and more specifically the species Toxocara canis and Toxocara cati. Also discussed is the discovery of the persistence of these larvae in the tissues of paratenic hosts, and the role that other species of this genus might or could play in other such hosts; including those where the life cycle has been described, i.e., Toxocara vitulorum, Toxocara pteropodis, Toxocara mackerrasae, and Toxocara tanuki. Also examined is the work that led to the realization that the larval stage leaving the egg actually being a third rather than a second stage larva. Also discussed on the work showing that the larvae can persist in paratenic host with remarkable longevity without undergoing any morphological change for years and that these larvae can be transmitted from one paratenic host to another by ingestion. People are usually infected by the ingestion of eggs containing third-stage larvae, but infections also occur on occasions from the ingestion of uncooked paratenic hosts.

Foliculitis por larvas de nematodo: una infrecuente causa de foliculitis en viajeros / Hookworm: An Uncommon Cause of Folliculitis in Travelers

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Autochthonous Cutaneous Larva Migrans in France and Europe.

Cutaneous larva migrans is a dermatitis, typically acquired in warm tropical or sub-tropical countries, caused by migration of the larvae of nematodes (hookworm; mainly Ancylostoma braziliense and, occasionally, Ancylostoma caninum or Uncinaria stenocephala), which are parasitic on animals such as cats and dogs, into the patient's skin. The larvae penetrate the skin after contact with infected soil and cause a typical creeping eruption. Patients with cutaneous larva migrans seen in Europe have usually acquired the disease following a stay in a tropical or sub-tropical area. How-ever, some cases of cutaneous larval migrans are acquired in Europe. We report here 5 autochthonous cases in France and give an overview of European autochthonous cases.

Epidemiology and morbidity of hookworm-related cutaneous larva migrans (HrCLM): Results of a cohort study over a period of six months in a resource-poor community in Manaus, Brazil.

BACKGROUND: Hookworm-related cutaneous larva migrans (HrCLM) is a neglected parasitic skin disease, widespread in resource-poor communities in tropical and subtropical countries. Incidence and risk factors have never been investigated in a cohort study. METHODOLOGY/PRINCIPAL FINDINGS: To understand the seasonal epidemiology of HrCLM, an open cohort of 476 children in a resource-poor community in Manaus, Brazil was examined for HrCLM monthly over a period of 6 months. Monthly prevalence and intensity of infection were correlated with the amount of monthly precipitation. Multivariable Cox regression analysis indicated male sex (hazard ratio [HR] 3.29; 95% confidence interval [CI] 1.95-5.56), walking barefoot on sandy ground (HR 2.30; 95% CI 1.03-5.16), poverty (HR 2.13; 95% CI 1.09-4.17) and age between 10 and 14 years (HR 1.87; 95% CI 1.01-3.46) as predictors of HrCLM. Monthly incidence rates ranged between 0.21 and 1.05 cases per person-year with an overall incidence of 0.52 per person-year. CONCLUSIONS/SIGNIFICANCE: HrCLM is a frequent parasitic skin disease in this resource-poor community. Every second child theoretically becomes infected during one year. Boys, 10 to 14 years old, belonging to the poorest households of the community, are the most vulnerable population group. Even in the tropical monsoonal climate of Amazonia there is a considerable seasonal variation with monthly incidence and number of lesions peaking in the rainy season.

Larva Migrans of Baylisascaris potosis In Experimental Animals.

Occurrence of clinical signs by infection with Baylisascaris potosis, the roundworm of kinkajous ( Potos flavus), in mice, rats, and rabbit were studied, and the migration behavior of larvae in mice were compared with that of Baylisascaris transfuga, the roundworm of bears ( Ursus spp.). Three groups of 8 mice, 3 groups of 6 rats, and 3 groups of 2 rabbits were inoculated with either 10, 100, or 1,000 B. potosis eggs. The other 8 mice were inoculated with 1,000 B. transfuga eggs. Animals were monitored for the occurrence of clinical signs until 60 days postinoculation (DPI). The carcass, viscera, brain, and eyes of each of 6 mice inoculated with 1,000 eggs of B. potosis or B. transfuga at 60 DPI were removed individually, and the number of larvae was counted. One mouse inoculated with 100 B. potosis eggs showed rolling at 27 DPI, and 1 larva was found in the medulla oblongata of this mouse. No clinical signs were observed in the other mice or in the rats and rabbits. A mean of 387.2 larvae was recovered from mice inoculated with 1,000 B. potosis eggs, and a mean of 422.0 larvae from mice inoculated with 1,000 B. transfuga eggs. The highest number of larvae was recovered from the carcasses for both B. potosis and B. transfuga. In the viscera, higher numbers of B. transfuga larvae (mean 131.8) were seen than B. potosis larvae (mean 33.1). In the brain, only 1 larva was detected in 1/6 mice inoculated with 1,000 B. potosis eggs, whereas a mean of 21 larvae was detected in mice inoculated with 1,000 B. transfuga eggs. A few larvae (range 0-1) were detected in the eyes of both mice inoculated with B. potosis or B. transfuga eggs. The result indicated that B. potosis larvae do not show a higher tendency to migrate into the brain of mice than B. transfuga larvae. However, 1 mouse inoculated with 100 eggs had 1 larva in the central nervous system and showed a serious neurological sign. This result may underline a potential risk of B. potosis to cause neural larva migrans in humans.

A modified method for molecular identification of Baylisascaris transfuga in European brown bears (Ursus arctos).

Baylisascaris transfuga is a roundworm that has been reported worldwide in most bear species. In mammals and possibly humans, the larvae of B. transfuga can migrate in the tissues of aberrant hosts with larva migrans syndrome. The current study was performed to identify B. transfuga in faecal samples from free-ranging brown bears in the Tatra Mountains National Park in southern Poland. A commercial kit was used to extract genomic DNA directly from faecal samples. Additionally, a Chelex resin-based technique was successfully implemented to prepare a PCR template from eggs retrieved by flotation. Based on the flotation results of 32 collected faecal samples, the prevalence of B. transfuga was 15.6%. The parasite was confirmed in samples found to be positive during the initial flotation by a molecular assay using DNA isolated directly from faeces. The retrieved eggs were confirmed as B. transfuga after their DNA was extracted using the Chelex protocol. Based on PCR amplification and sequencing of a 413-bp segment of cytochrome c oxidase 1 (COI), the obtained sequence was 100% identical to the COI segment of B. transfuga after a BLAST comparison to the GenBank™ database. The current study includes the first molecular confirmation of B. transfuga in brown bears in the western part of the Carpathians. We show that direct extraction of parasite DNA from bear faeces is efficient for molecular assays. As an alternative, we present the effectiveness of a Chelex-based technique for fast and convenient DNA isolation from the difficult-to-disrupt eggs of B. transfuga for PCR. Molecular tests of parasite DNA extracted directly from faecal material have limits of detection related to the amount of eggs in the samples. Thus, using classical flotation to obtain eggs for PCR may increase the credibility of the results, particularly in cases with a low number of excreted eggs. The Chelex resin protocol has potential for application in studies of intestinal parasites in wildlife for which conventional flotation is routinely used for microscopy.

Bullous cutaneous larva migrans: case series and review of atypical clinical presentations.

Hookworm-related cutaneous larva migrans (HRCLM) is caused by the penetration and migration in the epidermis of larvae of Ancylostoma braziliense and Ancylostoma caninum. It is characterized by slightly raised and erythematous tracks, located especially on the feet. These tracks may be single or multiple, serpiginous or linear, ramified and intertwined, accompanied by pruritus. Atypical clinical presentations of HRCLM are currently more frequent than in the past. We present six patients with bullous HRCLM and discuss the possible pathogenetic factors. Furthermore, we present a review of atypical clinical presentations of HRCLM. From 1998 to 2013 we observed approximately 180 patients with HRCLM. In all patients race, nationality, sex, age, country of infestation, location of the disease, clinical picture, laboratory and instrumental examinations and therapy were collected. In six patients (4 males and 2 females), we made a diagnosis, based on the history and clinical picture, of bullous HRCLM. The infestation was characterized by single or multiple blisters, round or oval in shape, of different size, with a clear serous fluid. Some tracks were also visible. All patients complained of pruritus. General physical examination and laboratory and instrumental examinations were normal or negative. Cytological examinations of the blisters showed the presence of lymphocytes and neutrophils, with numerous eosinophils. All patients were successfully treated with oral albendazole. Blisters appear because of the release by the larvae of lytic enzymes (metalloproteases and hyaluronidases). Furthermore, blisters might be the final clinical result of a delayed hypersensitivity reaction due to the release by larvae of unknown antigens. Finally, only in some patients, bullous HRCLM might represent an acute irritant/allergic contact dermatitis caused by topical drugs applied on the lesions. This hypothesis has been excluded in our patients because no topical treatment was made before our observation.

A Case of Furuncular Myiasis Due to Cordylobia anthropophaga in a Korean Traveler Returning from Uganda.

A fly larva was recovered from a boil-like lesion on the left leg of a 33-year-old male on 21 November 2016. He has worked in an endemic area of myiasis, Uganda, for 8 months and returned to Korea on 11 November 2016. The larva was identified as Cordylobia anthropophaga by morphological features, including the body shape, size, anterior end, posterior spiracles, and pattern of spines on the body. Subsequent 28S rRNA gene sequencing showed 99.9% similarity (916/917 bp) with the partial 28S rRNA gene of C. anthropophaga. This is the first imported case of furuncular myiasis caused by C. anthropophaga in a Korean overseas traveler.

Epidemiological profile of cutaneous larva migrans in travelers returning to France between 2003 and 2015.

BACKGROUND: Cutaneous larva migrans (CLM) is caused by the penetration and migration of canine or feline hookworm larvae into the skin, and frequently affects travelers from high-income countries returning from tropical and sub-tropical areas. Unfortunately, this pathology is neglected due to poor understanding among both physicians and travelers. This study describes the profile of cases reported in Marseille, France. PATIENTS AND METHODS: A retrospective study was performed in two specialized hospitals between 2003 and 2015. Data on socio-demographics, clinical aspects and treatment were collected. Diagnosis was based on travel history and symptoms. RESULTS: Forty-three patients with a diagnosis of CLM were recorded in this study. They were aged between 14 and 70 and 51% were male. They were infected while visiting the Americas (37%), Africa (33%), Asia (28%) and (in the case of one patient) Portugal. The mean timescale for diagnosis was 41 days. Track lesions associated with pruritus in the lower limbs were the most common symptoms. Nine had a history of super-infection. Sixteen patients received treatment prior to referral including six who were administered antiparasitic drugs. A one-day treatment with ivermectin, administered at our facility, resulted, in most instances, in a favorable outcome. CONCLUSION: This study reports 43 cases of CLM acquired mainly in Africa, Asia and the Americas but also, for the first time, CLM acquired during travel to Portugal. The data show the need for increased awareness of CLM prevention and treatment in order to optimize pre-travel advice and case management. Travelers need to understand how CLM is transmitted and the need to avoid contact with soil and sand contaminated by dogs and cats. In particular, footwear and sun chairs should be used on beaches.

BAYLISASCARIS PROCYONIS LARVA MIGRANS IN TWO CAPTIVE NORTH AMERICAN BEAVERS (CASTOR CANADENSIS).

Baylisascaris procyonis larva migrans was diagnosed in two North American beavers ( Castor canadensis ) belonging to a zoological park in Clarke County, Georgia. Both beavers presented with neurological signs. One beaver died naturally and despite attempted treatment, the other beaver was euthanatized because of severe clinical signs and poor prognosis. Histologic evaluation of the beavers revealed evidence of parasitic migration characterized by several lesions, including eosinophilic granulomas in various organs, as well as necrotizing eosinophilic and lymphoplasmacytic to granulomatous polioencephalitis, leukoencephalitis and cervical leukomyelitis. This represents the first confirmed case of B. procyonis larva migrans in beaver and the first non-raccoon ( Procyon lotor ) host in the southeastern United States. This report highlights the need for clinicians and diagnosticians to consider baylisascariasis in animals with compatible clinical signs. Preventative measures should be considered for captive animals, because early diagnosis of B. procyonis is challenging, and treatment is often unrewarding.

Cutaneous Larva Migrans Associated With Löffler's Syndrome in a 6-Year-Old Boy.

Cutaneous larva migrans is a frequent dermatologic problem among travelers in tropical areas, but its association with Löffler's syndrome is an extremely rare condition, particularly in children. Here, we describe a 6-year-old boy presenting cutaneous larva migrans associated with Löffler's syndrome.

Larva migrans syndrome caused by Toxocara and Ascaris roundworm infections in Japanese patients.

Larva migrans syndrome (LMS) caused by Toxocara and Ascaris roundworms is generally believed to be more common in children, while a report from Japan suggests that it is more common in adults. We conducted a large-scale retrospective study to confirm these findings and to clarify what caused the difference between Japan and other countries, to reveal overlooked aspects of this disease. The clinical information of 911 cases which we diagnosed as Toxocara or Ascaris LMS during 2001 and 2015 was analysed. Information used included age, sex, address (city or county), chief complaint, present history, dietary history, overseas travelling history, medical imaging findings and laboratory data (white blood cell count, peripheral blood eosinophil number and total IgE). The sex ratio of the disease was 2.37 (male/female = 641/270). The number of patients not younger than 20 years old were 97.8 and 95.1 % among males and females, respectively. Major disease types were visceral, ocular, neural and asymptomatic. The visceral type was more prevalent in older patients, while younger patients were more vulnerable to ocular symptoms. More than two-thirds of the patients whose dietary habits were recorded had a history of ingesting raw or undercooked animal meat. LMS caused by Toxocara or Ascaris is primarily a disease of adult males in Japan, who probably acquired infections by eating raw or undercooked animal meat/liver. Healthcare specialists should draw public attention to the risk of raw or undercooked animal meat in Europe as well.

[Cutaneous larva migrans syndrome on a malformed foot (a case report)]. / Syndrome de larva migrans cutanée sur pied malformé (à propos d'un cas).

Cutaneous larva migrans syndrome is a subcutaneous dermatitis caused by hookworms' larvae, originating from animals in parasitic impasse in humans. Transcutaneous infestation is favored by contact with contaminated soil. We report the case of a 15-month-old child, native of Guinea - Bissau, suffering from cutaneous larva migrans syndrome on a malformed foot. This malformation in the form of a syndactyly, associated with a tumefaction of the foot cause a delay in the standing position. Besides, the fact that the child never wears shoes because of the sick foot is another factor contributing to the patient's infestation by the larvae of the nematode.

[Cutaneous larva migrans: report of three cases from the Western Black Sea Region, Turkey]. / Kütanöz larva migrans: Bati Karadeniz Bölgesi'nden üç olgu sunumu.

Cutaneous larva migrans (CLM) is a parasitosis frequently seen in persons who have travelled to tropical or subtropical regions and in those who have worked in contact with soil. The disease frequently develops due to Ancylostoma braziliensis and Ancylostoma caninum species. After penetrating the skin and entering the body, the hookworm larva proceeds to bore tunnels through the epidermis, creating pruritic, erythematous, serpiginous lesions. Secondary bacterial infections of the lesions can often be seen, especially on the legs and buttocks. In this article we presented three atypical local cases which have not been declared previously in our country. The first case, a 54-year-old male who was admitted to hospital in August with complaints of an obverse body rash and itching lasting for a week. Eruptions were observed over a small area on the right side of the abdomen, consisting of itchy, raised, erythematous, curvilinear string-like lesions. Moreover, no eosinophilia was detected in the patient, whose culture showed a growth of Streptococcus pyogenes. The patient was clinically diagnosed with CLM accompanied by secondary bacterial infection and treated for three days with 1 g of amoxicillin-clavulanic acid, mupirocin cream and albendazole 400 mg/d. Under this regime, the lesions were seen to decline. The second case, a 38-year-old male was also admitted in August, complaining of itching and redness on his body. The patient, whose blood count values were normal, exhibited itchy, raised, serpiginous string-like lesions located on the left side of his body. The patient, whose bacterial culture was negative, was clinically diagnosed as CLM and treated for three days with albendazole 400 mg/d and the lesions were seen to improve. The third case, a 23-year old male was admitted in September complaining of itching and redness on his neck. An itchy, crescent-shaped erythematous lesion was detected on his neck; bacteriological cultures and blood count were normal. The common feature for all three cases was the story of working in a hazelnut orchard and mowing weeds using a motorized string trimmer (weed whacker). None of them had a history of travel outside the country. Therefore CLM assumed to be occurred due to the aeration of surface earth layer with the force of motorized string trimmer and entrance of the larvae were from the open parts of the body. In conclusion, it should be keep in mind that hookworm larva-related CLM can be encountered in our country, and reporting of the patients with similar findings are necessary to determine the prevalence of this parasitosis in our country.