In vitro efficacy of essential oils against various Candida species.

Candida species are responsible for the most common fungal infections worldwide. We studied the in vitro antifungal activity of a large panel of essential oils (EOs) against various Candida species. The EOs activity against Candida spp. was tested using a gradient microdilution assay ranging from 4% to 0.008% (v/v). After a preliminary screening including 31 EOs, seven selected EOs were tested against 13 clinical isolates and four reference strains belonging to six Candida species. Cinnamomum zeylanicum and Cymbopogon giganteus EOs exhibited the best antifungal activity against all clinical and reference strains, with MIC ranges of 0.015%-0.25% (v/v). EOs from Litsea citrata, Backhousia citriodora and Ocimum sanctum presented MIC ranges of 0.03%-0.5% (v/v). The antifungal efficacy of EOs was independent of the susceptibility of Candida strains to usual antifungal agents. These EOs could have a promising antifungal action.

In vitro efficacy of essential oils against Sarcoptes scabiei.

The mite Sarcoptes scabiei is responsible for scabies, a pruritic and contagious skin disease in humans. S. scabiei is also responsible for mange in a wide range of animal species. The treatment of S. scabiei infection is hampered by an under-effectiveness of the few available drugs. The objective of this work was to evaluate the in vitro acaricide activity of a large number of plant essential oils (EOs) against S. scabiei. EOs were selected mainly on the basis of traditional treatments for dermatological infections in Madagascar. The sarcoptes originating from a porcine animal model were tested at concentrations ranging from 10 to 0.1%. The viability of sarcoptes was assessed by stereomicroscopic observation at 5 min, 15 min, 30 min, 45 min and then every hour until 6 h after treatment. Estimates of lethal time and lethal concentration producing 50% mortality were generated using a probit analysis. The survival curves were estimated using the Kaplan Meier method. A total of 31 EOs from different plants were tested. Cinnamomum zeylanicum (cinnamom) and Ocimum sanctum (tulsi) oils were the most active for all concentrations tested. They may be included in in vivo studies, in order to further assess their potential interest as topical treatments.

The Potential of 2-Substituted Quinolines as Antileishmanial Drug Candidates.

There is a need for new, cost-effective drugs to treat leishmaniasis. A strategy based on traditional medicine practiced in Bolivia led to the discovery of the 2-substituted quinoline series as a source of molecules with antileishmanial activity and low toxicity. This review documents the development of the series from the first isolated natural compounds through several hundred synthetized molecules to an optimized compound exhibiting an in vitro IC50 value of 0.2 µM against Leishmania donovani, and a selectivity index value of 187, together with in vivo activity on the L. donovani/hamster model. Attempts to establish structure-activity relationships are described, as well as studies that have attempted to determine the mechanism of action. For the latter, it appears that molecules of this series act on multiple targets, possibly including the immune system, which could explain the observed lack of drug resistance after in vitro drug pressure. We also show how nanotechnology strategies could valorize these drugs through adapted formulations and how a mechanistic targeting approach could generate new compounds with increased activity.

Autochthonous Gnathostomiasis in Madagascar.

We used molecular tools to identify an autochthonous case of gnathostomiasis in Madagascar. This severe ocular infection, caused by Gnathostoma spinigerum nematodes, led to vision loss in the patient's left eye. Clinicians should be aware of this parasitosis in Madagascar and other countries in Africa.

Bed Bugs (Hemiptera, Cimicidae): Overview of Classification, Evolution and Dispersion.

The bed bugs (Cimex lectularius and C. hemipterus) have undergone a significant resurgence worldwide since the 1990s. A compilation of findings from a database, including 2650 scientific publications from seven major medical databases, allowed us to document main evolutionary events, from fossil evidence, dating from 11,000 years ago, until the present that has led to the current worldwide expansion of Cimicid species. We present the hypotheses on the possible dispersion pathways of bed bugs in light of the major historical and evolutionary events. A detailed classification of the Cimicidae family and finally, an illustrative map displaying the current distribution of known Cimex species in each geographical ecozone of Asia, Europe, Africa, the Americas, and Australia are presented.

Essential Oils as a Potential Treatment Option for Pediculosis.

Pediculosis is a prevalent ectoparasite infestation caused by lice. The head louse (Pediculus humanus capitis) and body louse (Pediculus humanus humanus) are obligatory parasites whose only known hosts are humans. Pediculosis is probably the most common ectoparasitic infestation, affecting up to 80% of the population in several countries, and particularly prevalent in the infant population worldwide. Several treatment options, including shampoos and creams containing insecticides, have been introduced for the treatment of pediculosis. Recently, the use of synthetic chemicals to control human lice has raised concerns pertaining to human health and the environment. Therefore, increasing efforts have been undertaken to develop effective pediculicides with low environmental toxicity and minimal environmental residual activity. In this study, we focus on the essential oils derived from 22 plant genera, their constituents, and the major factors that play important roles in the effectiveness of these oils in the treatment of pediculosis. Furthermore, we discuss the advantages and limitations of the mentioned essential oils, and ultimately suggest those demonstrating the most effective in vitro pediculicidal activities. The genera such as Aloysia, Cinnamomum, Eucalyptus, Eugenia, Lavandula, Melaleuca, Mentha, Myrcianthes, Origanum, Pimpinella, and Thymus appear to be more efficient against lice. These genera are rich in anethole, 1,8-cineole, cinnamaldehyde, p-cymene, eugenol, linalool, limonene, pulegone, terpinen-4-ol, and thymol compounds.

Plasmodium vivax severe imported malaria in two migrants in France.

BACKGROUND: With less than one severe case per year in average, Plasmodium vivax is very rarely associated with severe imported malaria in France. Two cases of P. vivax severe malaria occurred in patients with no evident co-morbidity. Interestingly, both cases did not occur at the primary infection but during relapses. CASE PRESENTATIONS: Patient 1: A 27-year old male, born in Afghanistan and living in France since 2012, was admitted on August 2015 to the Avicenne hospital because of abdominal pain, intense headache, fever and hypotension. The patient was haemodynamically unstable despite 5 L of filling solution. A thin blood film showed P. vivax trophozoites within the red blood cells. To take care of the septic shock, the patient was given rapid fluid resuscitation, norepinephrine (0.5 mg/h), and intravenous artesunate. Nested polymerase chain reactions of the SSUrRNA gene were negative for Plasmodium falciparum but positive for P. vivax. The patient became apyretic in less than 24H and the parasitaemia was negative at the same time. Patient 2: A 24-year old male, born in Pakistan and living in France, was admitted on August 2016 because of fever, abdominal pain, headache, myalgia, and nausea. The last travel of the patient in a malaria endemic area occurred in 2013. A thin blood film showed P. vivax trophozoites within the red blood cells. The patient was treated orally by dihydroartemisinin-piperaquine and recovered rapidly. Nine months later, the patient returned to the hospital with a relapse of P. vivax malaria. The malaria episode was uncomplicated and the patient recovered rapidly. Three months later, the patient came back again with a third episode of P. vivax malaria. Following a rapid haemodynamic deterioration, the patient was transferred to the intensive care unit of the hospital. In all the patient received 10 L of filling solution to manage the septic shock. After 5 days of hospitalization and a specific treatment, the patient was discharged in good clinical conditions. CONCLUSION: Clinicians should be aware of the potential severe complications associated with P. vivax in imported malaria, even though the primary infection is uncomplicated.

Molecular Survey of Head and Body Lice, Pediculus humanus, in France.

Human lice, Pediculus humanus, are obligate blood-sucking parasites. Phylogenetically, they belong to several mitochondrial clades exhibiting some geographic differences. Currently, the body louse is the only recognized disease vector, with the head louse being proposed as an additional vector. In this article, we study the genetic diversity of head and body lice collected from Bobigny, a town located close to Paris (France), and look for louse-borne pathogens. By amplifying and sequencing the cytb gene, we confirmed the presence of clades A and B in France. Besides, by amplifying and sequencing both cytb and cox1 gene, we reported, for the first time, the presence of clade E, which has thus far only been found in lice from West Africa. DNA from Bartonella quintana was detected in 16.7% of body lice from homeless individuals, but in none of the head lice collected from 47 families. Acinetobacter DNA was detected in 11.5% of head lice belonging to all three clades and 29.1% of body lice. Six species of Acinetobacter were identified, including two potential new ones. Acinetobacter baumannii was the most prevalent, followed by Candidatus Acinetobacter Bobigny-1, Acinetobacter calcoaceticus, Acinetobacter nosocomialis, Acinetobacter junii, and Candidatus Acinetobacter Bobigny-2. Body lice were found to be infected only with A. baumannii. These findings show for the first time, the presence of clade E head lice in France. This study is also the first to report the presence of DNAs of several species of Acinetobacter in human head lice in France.

Do drowning and anoxia kill head lice?

Chemical, physical, and mechanical methods are used to control human lice. Attempts have been made to eradicate head lice Pediculus humanus capitis by hot air, soaking in various fluids or asphyxiation using occlusive treatments. In this study, we assessed the maximum time that head lice can survive anoxia (oxygen deprivation) and their ability to survive prolonged water immersion. We also observed the ingress of fluids across louse tracheae and spiracle characteristics contrasting with those described in the literature. We showed that 100% of lice can withstand 8 h of anoxia and 12.2% survived 14 h of anoxia; survival was 48.9% in the untreated control group at 14 h. However, all lice had died following 16 h of anoxia. In contrast, the survival rate of water-immersed lice was significantly higher when compared with non-immersed lice after 6 h (100% vs. 76.6%, p = 0.0037), and 24 h (50.9% vs. 15.9%, p = 0.0003). Although water-immersed lice did not close their spiracles, water did not penetrate into the respiratory system. In contrast, immersion in colored dimeticone/cyclomethicone or colored ethanol resulted in penetration through the spiracles and spreading to the entire respiratory system within 30 min, leading to death in 100% of the lice.

In vitro efficacy of five essential oils against Pediculus humanus capitis.

Treatment of head lice has relied mainly on the use of topical insecticides. Today, conventional topical pediculicides have suffered considerable loss of activity worldwide. There is increasing interest in the use of natural products such as essential oils for head louse control, and many of them are now incorporated into various over-the-counter products presented as pediculicides, often without proper evaluation. The aim of the present study was to assess the in vitro efficacy of five essential oils against adults of Pediculus humanus capitis using a contact filter paper toxicity bioassay. The chemical composition of the essential oils from wild bergamot, clove, lavender, tea tree, and Yunnan verbena was analyzed by gas chromatography-mass spectrometry. All treatments and controls were replicated three times on separate occasions over a period of 11 months. In all, 1239 living lice were collected from the scalp of 51 subjects, aged from 1 to 69 years. Clove oil, diluted either in coco oil or sunflower oil, demonstrated the best adulticidal activity, reaching > 90% mortality within 2 h in lice submitted to a 30-min contact. Yunnan verbena oil diluted in coco oil showed also a significant efficacy. Other essential oils showed a lower efficacy. The oil's major component(s) differed according to the tested oils and appeared chemically diverse. In the case of clove oil, the eugenol appeared as the main component. This study confirmed the potential interest of some of the essential oils tested, but not all, as products to include possibly in a pediculicidal formulation.

Correction to: Imported falciparum malaria in adults: host- and parasite-related factors associated with severity. The French prospective multicenter PALUREA cohort study.

The members of the Palurea Study Group were provided in such a way that they could not be indexed as collaborators on PubMed. The publisher apologizes for this error and is pleased to list the members of the group here.

In vitro activity of ten essential oils against Sarcoptes scabiei.

BACKGROUND: The development of alternative approaches in ectoparasite management is currently required. Essential oils have been demonstrated to exhibit fumigant and topical toxicity to a number of arthropods. The aim of the present study was to assess the potential efficacy of ten essential oils against Sarcoptes scabiei. METHODS: The major chemical components of the oils were identified by GC-MS analysis. Contact and fumigation bioassays were performed on Sarcoptes mites collected from experimentally infected pigs. For contact bioassays, essential oils were diluted with paraffin to get concentrations at 10, 5, and even 1% for the most efficient ones. The mites were inspected under a stereomicroscope 10, 20, 30, 40, 50, 60, 90, 120, 150, and 180min after contact. For fumigation bioassay, a filter paper was treated with 100 µL of the pure essential oil. The mites were inspected under a stereomicroscope for the first 5min, and then every 5min until 1h. RESULTS: Using contact bioassays, 1% clove and palmarosa oil killed all the mites within 20 and 50min, respectively. The oils efficacy order was: clove > palmarosa > geranium > tea tree > lavender > manuka > bitter orange > eucalyptus > Japanese cedar. In fumigation bioassays, the efficacy order was: tea tree > clove > eucalyptus > lavender > palmarosa > geranium > Japanese cedar > bitter orange > manuka. In both bioassays, cade oil showed no activity. CONCLUSION: Essential oils, especially tea tree, clove, palmarosa, and eucalyptus oils, are potential complementary or alternative products to treat S. scabiei infections in humans or animals, as well as to control the mites in the environment.

Imported falciparum malaria in adults: host- and parasite-related factors associated with severity. The French prospective multicenter PALUREA cohort study.

PURPOSE: Prospective data on potential factors associated with severity of imported Plasmodium falciparum malaria are lacking. We evaluated whether several host- and parasite-related biomarkers may improve early severity evaluation. METHODS: Prospective multicenter observational study comparing uncomplicated and severe imported falciparum malaria in adults conducted in France in 52 units, from 2007 to 2010. Association of several host- and parasite-related biomarkers with severity of malaria was tested using univariate and multivariate analyses. RESULTS: Of 295 patients, 140 had uncomplicated malaria and 155 severe malaria (including very severe and less severe cases according to predefined criteria). Curative intravenous quinine treatment was used in 154/155 patients with severe malaria and atovaquone/proguanil in 74 % of patients with uncomplicated malaria. Hospital mortality was 5.2 % (8 patients), all in the severe malaria group. Among host-related biomarkers, CRP, procalcitonin, and sTREM-1 were significantly higher and albumin was significantly lower in severe versus uncomplicated malaria; only the last three biomarkers also differed significantly between the very and less severe malaria groups. Among parasite-related biomarkers, only plasma PfHRP2 was significantly higher in severe versus uncomplicated malaria and in very severe versus less severe malaria; parasitemia did not differ between very and less severe malaria. By multivariate analysis, only lower plasma albumin and higher sTREM-1 were associated with greater severity, with intermediate accuracies. CONCLUSIONS: During imported malaria, the most useful biomarkers associated with severity seem to be plasma albumin and sTREM-1; and among parasite-related parameters, PfHRP2 was more strongly associated with severity than parasitemia was.

Are humans the initial source of canine mange?

BACKGROUND: Scabies, or mange as it is called in animals, is an ectoparasitic contagious infestation caused by the mite Sarcoptes scabiei. Sarcoptic mange is an important veterinary disease leading to significant morbidity and mortality in wild and domestic animals. A widely accepted hypothesis, though never substantiated by factual data, suggests that humans were the initial source of the animal contamination. In this study we performed phylogenetic analyses of populations of S. scabiei from humans and from canids to validate or not the hypothesis of a human origin of the mites infecting domestic dogs. METHODS: Mites from dogs and foxes were obtained from three French sites and from other countries. A part of cytochrome c oxidase subunit 1 (cox1) gene was amplified and directly sequenced. Other sequences corresponding to mites from humans, raccoon dogs, foxes, jackal and dogs from various geographical areas were retrieved from GenBank. Phylogenetic analyses were performed using the Otodectes cynotis cox1 sequence as outgroup. Maximum Likelihood and Bayesian Inference analysis approaches were used. To visualize the relationship between the haplotypes, a median joining haplotype network was constructed using Network v4.6 according to host. RESULTS: Twenty-one haplotypes were observed among mites collected from five different host species, including humans and canids from nine geographical areas. The phylogenetic trees based on Maximum Likelihood and Bayesian Inference analyses showed similar topologies with few differences in node support values. The results were not consistent with a human origin of S. scabiei mites in dogs and, on the contrary, did not exclude the opposite hypothesis of a host switch from dogs to humans. CONCLUSIONS: Phylogenetic relatedness may have an impact in terms of epidemiological control strategy. Our results and other recent studies suggest to re-evaluate the level of transmission between domestic dogs and humans.

Efficacy assessment of biocides or repellents for the control of Sarcoptes scabiei in the environment.

BACKGROUND: Sarcoptes scabiei infection is a contagious disease affecting both humans and animals. The transmission occurs either by direct contact or from the environment where mites could survive several days remaining infective. The number of products available for environmental control of S. scabiei is very limited. The objective of the present study was to assess the efficacy of biocides or repellents against S. scabiei var suis. METHODS: Tested products included pyrethroids: permethrin, esdepallethrin and bioresmethrin, bifenthrin, cypermethrin and imiprothrin, cyfluthrin, tetramethrin and sumithrin. We also tested repellents: DEET, icaridin and IR3535. Sarcoptes scabiei var suis mites were collected from experimentally-infected pigs. For each test, 20 live mites of all motile stages were placed in a plastic Petri dish and sprayed uniformly by each product. Control mites were sprayed by distilled water. The study was performed in triplicate under room conditions and the mites were inspected under a stereomicroscope at intervals (5, 10, 15, 20, 25, 30, 40, 50, 60 min, 2, 3, 4, 5 and 24 h) after exposure to the products. RESULTS: All the products, except the combination of tetramethrin and sumithrin (A-PAR), were able to kill all mites within 24 h. The median survival time was 50 ± 30.4 min, 120 ± 309 min, 10 ± 5.9 min, 40 ± 36.8 min, 15 ± 7.3 min, 180 ± 417 min and 1440 ± 600 min when mites were exposed to permethrin 4 %, permethrin 0.6%, esdepallethrin and bioresmethrin, bifenthrin, cypermethrin and imiprothrin, cyfluthrin, tetramethrin and sumithrin, respectively. The median survival time was 20 ± 6.5 min, 15 ± 4.3 min, 30 ± 42.1 min and 15 ± 4.9 min for DEET 25, DEET 50, icaridin 20 and IR3535 20%, respectively. CONCLUSIONS: The results of the present study could support evidence-based use of biocides and repellents in households, hospitals and farms.

Immunoglobulin response to Plasmodium falciparum RESA proteins in uncomplicated and severe malaria.

BACKGROUND: The three members of the ring-infected erythrocyte surface antigen (RESA) proteins family share high sequence homologies, which impair the detection and assignment to one or another protein of some pathogenic processes inherent to Plasmodium falciparum malaria. The present study was intended to determine if the antibody and inflammatory responses of children living in a malaria-endemic area varied depending on the RESA-1, RESA-2 or RESA-3 proteins and the severity of the disease, two groups of severe and uncomplicated malaria cases being considered. METHODS: Two synthetic peptides representing predicted B cell epitopes were designed per RESA protein, all located outside of the 3' and 5' repetition blocks, in order to allow an antibody detection specific of each member of the family. Recombinant rRESA-1B and rRESA-3B proteins were also engineered. Two groups of Beninese children admitted to hospital in 2009 for either uncomplicated or severe malaria were compared for their plasma levels of IgG specifically recognizing each recombinant RESA protein or synthetic peptide, and for their plasma inflammatory cytokine levels (IFN-γ, TNF-α and IL-10), taking into account host and parasite genetic factors. RESULTS: The absence of IgG cross-reactivity between rRESA proteins and their protein carrier as well as between each RESA peptide and a non-epitopic RESA control peptide validated the use of the engineered recombinant proteins and peptides for the measurement of plasma IgG. Taking into account age, fever duration and parasitaemia, a multiple logistic regression performed on children clustered according to their antibody responses' profiles concluded to an increased risk of severe malaria for P2 (representative of RESA-1) responders (P = 0.007). Increased IL-10 plasma levels were found in children harbouring multiclonal P. falciparum infections on the basis of the T1526G resa2 gene polymorphism (P = 0.004). CONCLUSIONS: This study provided novel tools to dissect the seroreactivity against the three members of the RESA protein family and to describe its relation to protection against malaria. It suggested the measurement of plasma antibodies raised against specific peptides to serve as predictive immunologic markers for disease severity. Lastly, it reinforced previous observations linking the T1526G resa2 gene mutation to severe malaria.

Effects of mefloquine use on Plasmodium vivax multidrug resistance.

Numerous studies have indicated a strong association between amplification of the multidrug resistance-1 gene and in vivo and in vitro mefloquine resistance of Plasmodium falciparum. Although falciparum infection usually is not treated with mefloquine, incorrect diagnosis, high frequency of undetected mixed infections, or relapses of P. vivax infection triggered by P. falciparum infections expose non-P. falciparum parasites to mefloquine. To assess the consequences of such unintentional treatments on P. vivax, we studied variations in number of Pvmdr-1 (PlasmoDB accession no. PVX_080100, NCBI reference sequence NC_009915.1) copies worldwide in 607 samples collected in areas with different histories of mefloquine use from residents and from travelers returning to France. Number of Pvmdr-1 copies correlated with drug use history. Treatment against P. falciparum exerts substantial collateral pressure against sympatric P. vivax, jeopardizing future use of mefloquine against P. vivax. A drug policy is needed that takes into consideration all co-endemic species of malaria parasites.