First detection of Leishmania major DNA in Sergentomyia (Spelaeomyia) darlingi from cutaneous leishmaniasis foci in Mali

Background

Leishmania major complex is the main causative agent of zoonotic cutaneous leishmaniasis (ZCL) in the Old World. Phlebotomus papatasi and Phlebotomus duboscqi are recognized vectors of L. major complex in Northern and Southern Sahara, respectively. In Mali, ZCL due to L. major is an emerging public health problem, with several cases reported from different parts of the country. The main objective of the present study was to identify the vectors of Leishmania major in the Bandiagara area, in Mali.

Methodology/Principal Findings

An entomological survey was carried out in the ZCL foci of Bandiagara area. Sandflies were collected using CDC miniature light traps and sticky papers. In the field, live female Phlebotomine sandflies were identified and examined for the presence of promastigotes. The remaining sandflies were identified morphologically and tested for Leishmania by PCR in the ITS2 gene. The source of blood meal of the engorged females was determined using the cyt-b sequence. Out of the 3,259 collected sandflies, 1,324 were identified morphologically, and consisted of 20 species, of which four belonged to the genus Phlebotomus and 16 to the genus Sergentomyia. Leishmania major DNA was detected by PCR in 7 of the 446 females (1.6%), specifically 2 out of 115 Phlebotomus duboscqi specimens, and 5 from 198 Sergentomyia darlingi specimens. Human DNA was detected in one blood-fed female S. darlingi positive for L. major DNA.

Conclusion

Our data suggest the possible involvement of P. duboscqi and potentially S. darlingi in the transmission of ZCL in Mali.     

Insecticide susceptibility of Phlebotomus argentipes in visceral leishmaniasis endemic districts in India and Nepal

Objectives

To investigate the DDT and deltamethrin susceptibility of Phlebotomus argentipes, the vector of Leishmania donovani, responsible for visceral leishmaniasis (VL), in two countries (India and Nepal) with different histories of insecticide exposure.

Methods

Standard WHO testing procedures were applied using 4% DDT and 0.05% deltamethrin impregnated papers. The effect of the physiological status (fed and unfed) of females on the outcome of the bioassays was assessed and the optimal time of exposure for deltamethrin was evaluated on a colony population. Field populations from both countries were tested.

Results

Fed and unfed females responded in a similar way. For exposure time on field samples 60 min was adopted for both DDT and deltamethrin. In Bihar, knockdown and mortality with DDT was respectively 20 and 43%. In Nepal almost all sand flies were killed, except at the border with Bihar (mortality 62%). With 0.05% deltamethrin, between 96 and 100% of the sand flies were killed in both regions.

Conclusions

Based on literature and present data 4% DDT and 0.05% deltamethrin seem to be acceptable discriminating concentrations to separate resistant from susceptible populations. Resistance to DDT was confirmed in Bihar and in a border village of Nepal, but the sand flies were still susceptible in villages more inside Nepal where only synthetic pyrethroids are used for indoor spraying. The low effectiveness of indoor spraying with DDT in Bihar to control VL can be partially explained by this resistance hence other classes of insecticides should be tested. In both countries P. argentipes sand flies were susceptible to deltamethrin.     

Immunity to distinct sand fly salivary proteins primes the anti-Leishmania immune response towards protection or exacerbation of disease

Background

Leishmania parasites are transmitted in the presence of sand fly saliva. Together with the parasite, the sand fly injects biologically active salivary components that favorably change the environment at the feeding site. Exposure to bites or to salivary proteins results in immunity specific to these components. Mice immunized with Phlebotomus papatasi salivary gland homogenate (SGH) or pre-exposed to uninfected bites were protected against Leishmania major infection delivered by needle inoculation with SGH or by infected sand fly bites. Immunization with individual salivary proteins of two sand fly species protected mice from L. major infection. Here, we analyze the immune response to distinct salivary proteins from P. papatasi that produced contrasting outcomes of L. major infection.

Methodology/Principal Findings

DNA immunization with distinct DTH-inducing salivary proteins from P. papatasi modulates L. major infection. PpSP15-immunized mice (PpSP15-mice) show lasting protection while PpSP44-immunized mice (PpSP44-mice) aggravate the infection, suggesting that immunization with these distinct molecules alters the course of anti-Leishmania immunity. Two weeks post-infection, 31.5% of CD4⁺ T cells produced IFN-γ in PpSP15-mice compared to 7.1% in PpSP44-mice. Moreover, IL-4-producing cells were 3-fold higher in PpSP44-mice. At an earlier time point of two hours after challenge with SGH and L. major, the expression profile of PpSP15-mice showed over 3-fold higher IFN-γ and IL-12-Rβ2 and 20-fold lower IL-4 expression relative to PpSP44-mice, suggesting that salivary proteins differentially prime anti-Leishmania immunity. This immune response is inducible by sand fly bites where PpSP15-mice showed a 3-fold higher IFN-γ and a 5-fold lower IL-4 expression compared with PpSP44-mice.

Conclusions/Significance

Immunization with two salivary proteins from P. papatasi, PpSP15 and PpSP44, produced distinct immune profiles that correlated with resistance or susceptibility to Leishmania infection. The demonstration for the first time that immunity to a defined salivary protein (PpSP44) results in disease enhancement stresses the importance of the proper selection of vector-based vaccine candidates.     

Hyaluronidase of bloodsucking insects and its enhancing effect on leishmania infection in mice

Background

Salivary hyaluronidases have been described in a few bloodsucking arthropods. However, very little is known about the presence of this enzyme in various bloodsucking insects and no data are available on its effect on transmitted microorganisms. Here, we studied hyaluronidase activity in thirteen bloodsucking insects belonging to four different orders. In addition, we assessed the effect of hyaluronidase coinoculation on the outcome of Leishmania major infection in BALB/c mice.

Principal Findings

High hyaluronidase activity was detected in several Diptera tested, namely deer fly Chrysops viduatus, blackflies Odagmia ornata and Eusimilium latipes, mosquito Culex quinquefasciatus, biting midge Culicoides kibunensis and sand fly Phlebotomus papatasi. Lower activity was detected in cat flea Ctenocephalides felis. No activity was found in kissing bug Rhodnius prolixus, mosquitoes Anopheles stephensi and Aedes aegypti, tse-tse fly Glossina fuscipes, stable fly Stomoxys calcitrans and human louse Pediculus humanus. Hyaluronidases of different insects vary substantially in their molecular weight, the structure of the molecule and the sensitivity to reducing conditions or sodium dodecyl sulphate. Hyaluronidase exacerbates skin lesions caused by Leishmania major; more severe lesions developed in mice where L. major promastigotes were coinjected with hyaluronidase.

Conclusions

High hyaluronidase activities seem to be essential for insects with pool-feeding mode, where they facilitate the enlargement of the feeding lesion and serve as a spreading factor for other pharmacologically active compounds present in saliva. As this enzyme is present in all Phlebotomus and Lutzomyia species studied to date, it seems to be one of the factors responsible for enhancing activity present in sand fly saliva. We propose that salivary hyaluronidase may facilitate the spread of other vector-borne microorganisms, especially those transmitted by insects with high hyaluronidase activity, namely blackflies (Simuliidae), biting midges (Ceratopogonidae) and horse flies (Tabanidae).     

Serological markers of sand fly exposure to evaluate insecticidal nets against visceral leishmaniasis in India and Nepal: a cluster-randomized trial

Background

Visceral leishmaniasis is the world'' second largest vector-borne parasitic killer and a neglected tropical disease, prevalent in poor communities. Long-lasting insecticidal nets (LNs) are a low cost proven vector intervention method for malaria control; however, their effectiveness against visceral leishmaniasis (VL) is unknown. This study quantified the effect of LNs on exposure to the sand fly vector of VL in India and Nepal during a two year community intervention trial.

Methods

As part of a paired-cluster randomized controlled clinical trial in VL-endemic regions of India and Nepal we tested the effect of LNs on sand fly biting by measuring the antibody response of subjects to the saliva of Leishmania donovani vector Phlebotomus argentipes and the sympatric (non-vector) Phlebotomus papatasi. Fifteen to 20 individuals above 15 years of age from 26 VL endemic clusters were asked to provide a blood sample at baseline, 12 and 24 months post-intervention.

Results

A total of 305 individuals were included in the study, 68 participants provided two blood samples and 237 gave three samples. A random effect linear regression model showed that cluster-wide distribution of LNs reduced exposure to P. argentipes by 12% at 12 months (effect 0.88; 95% CI 0.83–0.94) and 9% at 24 months (effect 0.91; 95% CI 0.80–1.02) in the intervention group compared to control adjusting for baseline values and pair. Similar results were obtained for P. papatasi.

Conclusions

This trial provides evidence that LNs have a limited effect on sand fly exposure in VL endemic communities in India and Nepal and supports the use of sand fly saliva antibodies as a marker to evaluate vector control interventions.     

First molecular epidemiological study of cutaneous leishmaniasis in Libya

Background

Cutaneous leishmaniasis (CL) is a major public health problem in Libya. The objective of this study was to investigate, for the first time, epidemiological features of CL outbreaks in Libya including molecular identification of parasites, the geographical distribution of cases and possible scenarios of parasite transmission.

Methodology/Principal Findings

We studied 450 patients that came from 49 areas distributed in 12 districts in north-west Libya. The patients'' ages ranged from 9 months to 87 years (median age 25 years); 54% of the cases were males. Skin scrapings spotted on glass slides were collected for molecular identification of causative agent. The ribosomal internal transcribed spacer 1 (ITS1) was amplified and subsequently characterized by restriction fragment length polymorphism (RFLP) analysis. In total, 195 samples were successfully identified of which 148 (75.9%) were Leishmania major, and 47 (24.1%) Leishmania tropica. CL cases infected with L. major were found in all CL areas whereas L. tropica cases came mainly from Al Jabal Al Gharbi (46.4%), Misrata (17.8%) and Tarhuna districts (10.7%). A trend of seasonality was noticed for the infections with L. major which showed a clear peak between November and January, but was less pronounced for infections by L. tropica.

Conclusion

The first molecular study on CL in Libya revealed that the disease is caused by L. major and L. tropica and the epidemiological patterns in the different foci were the same as in other Mediterranean foci of CL.     

Coarse-resolution Ecology of Etiological Agent,Vector, and Reservoirs of Zoonotic Cutaneous Leishmaniasis in Libya

Cutaneous leishmaniasis ranks among the tropical diseases least known and most neglected in Libya. World Health Organization reports recognized associations of Phlebotomus papatasi, Psammomys obesus, and Meriones spp., with transmission of zoonotic cutaneous leishmaniasis (ZCL; caused by Leishmania major) across Libya. Here, we map risk of ZCL infection based on occurrence records of L. major, P. papatasi, and four potential animal reservoirs (Meriones libycus, Meriones shawi, Psammomys obesus, and Gerbillus gerbillus). Ecological niche models identified limited risk areas for ZCL across the northern coast of the country; most species associated with ZCL transmission were confined to this same region, but some had ranges extending to central Libya. All ENM predictions were significant based on partial ROC tests. As a further evaluation of L. major ENM predictions, we compared predictions with 98 additional independent records provided by the Libyan National Centre for Disease Control (NCDC); all of these records fell inside the belt predicted as suitable for ZCL. We tested ecological niche similarity among vector, parasite, and reservoir species and could not reject any null hypotheses of niche similarity. Finally, we tested among possible combinations of vector and reservoir that could predict all recent human ZCL cases reported by NCDC; only three combinations could anticipate the distribution of human cases across the country.     

First Detection of Leishmania tropica DNA and Trypanosoma Species in Sergentomyia Sand Flies (Diptera: Psychodidae) from an Outbreak Area of Cutaneous Leishmaniasis in Ghana

Background

Leishmania major and an uncharacterized species have been reported from human patients in a cutaneous leishmaniasis (CL) outbreak area in Ghana. Reports from the area indicate the presence of anthropophilic Sergentomyia species that were found with Leishmania DNA.

Methodology/Principal Findings

In this study, we analyzed the Leishmania DNA positive sand fly pools by PCR-RFLP and ITS1 gene sequencing. The trypanosome was determined using the SSU rRNA gene sequence. We observed DNA of L. major, L. tropica and Trypanosoma species to be associated with the sand fly infections. This study provides the first detection of L. tropica DNA and Trypanosoma species as well as the confirmation of L. major DNA within Sergentomyia sand flies in Ghana and suggests that S. ingrami and S. hamoni are possible vectors of CL in the study area.

Conclusions/Significance

The detection of L. tropica DNA in this CL focus is a novel finding in Ghana as well as West Africa. In addition, the unexpected infection of Trypanosoma DNA within S. africana africana indicates that more attention is necessary when identifying parasitic organisms by PCR within sand fly vectors in Ghana and other areas where leishmaniasis is endemic.     

Exposure to Phlebotomus argentipes (Diptera,Psychodidae, Phlebotominae) Sand Flies in Rural Areas of Bihar,India: The Role of Housing Conditions

Background

Visceral Leishmaniasis (VL) is a vector-borne infectious disease, caused by the protozoan Leishmania donovani, which is transmitted by phlebotomine sand flies. In an earlier study in Bihar, India, we found an association between incidence of VL and housing conditions. In the current study we investigated the influence of housing structure and conditions in and around the house on the indoor abundance of Phlebotomus argentipes, the vector of VL in this area.

Methods

In each of 50 study villages in Muzaffarpur district, we randomly selected 10 houses. Light traps were installed in each house for one night during three annual peaks of sand fly density over two successive years. Sand flies captured were morphologically identified and segregated by species, sex and feeding status. Data on housing conditions and socio-economic status were also collected. We fitted a linear mixed-effects regression model with log-transformed P. argentipes counts as outcome variable and village as random effect.

Results

P. argentipes was found in all but four of the 500 households. There was considerable variability between the years and the seasons. On bivariate analysis, housing structure, dampness of the floor, keeping animals inside, presence of animal dung around the house, and socio-economic status were all significantly associated with sand fly density. Highest sand fly densities were observed in thatched houses. In the multivariate model only the housing structure and socio-economic status remained significant.

Conclusions

Better housing conditions are associated with lower sand fly densities, independent of other socio-economic conditions. However, in this area in Bihar even in the better-built houses sand flies are present.     

A fly in the ointment: evaluation of traditional use of plants to repel and kill blowfly larvae in fermented fish

Introduction

In rural areas in Laos, fly larvae infestations are common in fermenting fish. Blowflies (Chrysomya megacephala, Diptera: Calliphoridae) are attracted to oviposit (and/or larviposit) onto fermenting fish which results in infestations with fly larvae. Knowledge of traditional use of plants to repel larvae during the production of fermented fish is common and widespread in Lao PDR.

Research Questions

How effective are the most salient species in repelling, and killing fly larvae in fermenting fish?

Material and Methods

The three plant species most frequently reported to repel fly larvae during an ethnobotanical survey throughout Lao PDR were tested for repellence and larvicidal activity of fly larvae infesting fermented fish. The lethality and repellence of Tadehagi triquetrum (L.) H. Ohashi (Fabaceae), Uraria crinita (L.) Desv. ex DC. (Fabaceae) and Bambusa multiplex (Lour.) Raeusch. ex Schult. & Schult. f. (Poaceae) were tested in an experimental design using fermenting fish in Vientiane, Lao PDR.

Results

The repellent effect of fresh material of T. triquetrum and U. crinita, and the larvicidal effect of fresh B. multiplex, is significantly more effective than that of dried material of the same species, and the total effect (repellence and larvicidal effect combined) for each of the three species was significantly more effective for fresh than for dry material. Fresh material of T. triquetrum, U. crinita, or B. multiplex added on top of the fermenting fish repelled 50%, 54%, 37%, and killed 22%, 28%, and 40% of fly larvae. The total effect was not significantly different per species at 72%, 82%, and 77%, respectively.

Discussion and Conclusions

The three most salient species are effective in repelling and killing fly larvae in the production of fermented fish, and may be essential to augment food safety during traditional fermentation in open jars.     

Salivary Antigen SP32 Is the Immunodominant Target of the Antibody Response to Phlebotomus papatasi Bites in Humans

Background

Zoonotic cutaneous leishmaniasis (ZCL) due to Leishmania major is highly prevalent in Tunisia and is transmitted by a hematophagous vector Phlebotomus papatasi (P. papatasi). While probing for a blood meal, the sand fly injects saliva into the host''s skin, which contains a variety of compounds that are highly immunogenic. We recently showed that the presence of anti-saliva antibodies was associated with an enhanced risk for leishmaniasis and identified the immunodominant salivary protein of Phlebotomus papatasi as a protein of approximately 30 kDa.

Methodology/Principal Findings

We cloned and expressed in mammalian cells two salivary proteins PpSP30 and PpSP32 with predicted molecular weights close to 30 kDa from the Tunisian strain of P. papatasi. The two recombinant salivary proteins were purified by two-step HPLC (High-Performance Liquid Chromatography) and tested if these proteins correspond to the immunodominant antigen of 30 kDa previously shown to be recognized by human sera from endemic areas for ZCL and exposed naturally to P. papatasi bites. While recombinant PpSP30 (rPpSP30) was poorly recognized by human sera from endemic areas for ZCL, rPpSP32 was strongly recognized by the tested sera. The binding of human IgG antibodies to native PpSP32 was inhibited by the addition of rPpSP32. Consistently, experiments in mice showed that PpSP32 induced the highest levels of antibodies compared to other P. papatasi salivary molecules while PpSP30 did not induce any detectable levels of antibodies.

Conclusions

Our findings demonstrate that PpSP32 is the immunodominant target of the antibody response to P. papatasi saliva. They also indicate that the recombinant form of PpSP32 is similar to the native one and represents a good candidate for large scale testing of human exposure to P. papatasi bites and perhaps for assessing the risk of contracting the disease.     

Visualisation of Leishmania donovani fluorescent hybrids during early stage development in the sand fly vector

Background

The Leishmania protozoan parasites cause devastating human diseases. Leishmania have been considered to replicate clonally, without genetic exchange. However, an accumulation of evidence indicates that there are inter-specific and intra-specific hybrids among natural populations. The first and so far only experimental proof of genetic exchange was obtained in 2009 when double drug resistant Leishmania major hybrids were produced by co-infecting sand flies with two strains carrying different drug resistance markers. However, the location and timing of hybridisation events in sand flies has not been described.

Methodology/Principal Findings

Here we have co-infected Phlebotomus perniciosus and Lutzomyia longipalpis with transgenic promastigotes of Leishmania donovani strains carrying hygromycin or neomycin resistance genes and red or green fluorescent markers. Fed females were dissected at different times post bloodmeal (PBM) and examined by fluorescent microscopy or fluorescent activated cell sorting (FACS) followed by confocal microscopy. In mixed infections strains LEM3804 and Gebre-1 reached the cardia and stomodeal valves more rapidly than strains LEM4265 and LV9. Hybrids unequivocally expressing both red and green fluorescence were seen in single flies of both vectors tested, co-infected with LEM4265 and Gebre-1. The hybrids were present as short (procyclic) promastigotes 2 days PBM in the semi-digested blood in the endoperitrophic space. Recovery of a clearly co-expressing hybrid was also achieved by FACS. However, hybrids could not sustain growth in vitro.

Conclusions/Significance

For the first time, we observed L. donovani hybrids in the sand fly vector, 2 days PBM and described the morphological stages involved. Fluorescence microscopy in combination with FACS allows visualisation and recovery of the progeny of experimental crosses but on this occasion the hybrids were not viable in vitro. Nevertheless, genetic exchange in L. donovani has profound epidemiological significance, because it facilitates the emergence and spread of new phenotypic traits.     

KSAC, a defined Leishmania antigen, plus adjuvant protects against the virulence of L. major transmitted by its natural vector Phlebotomus duboscqi

Background

Recombinant KSAC and L110f are promising Leishmania vaccine candidates. Both antigens formulated in stable emulsions (SE) with the natural TLR4 agonist MPL® and L110f with the synthetic TLR4 agonist GLA in SE protected BALB/c mice against L. major infection following needle challenge. Considering the virulence of vector-transmitted Leishmania infections, we vaccinated BALB/c mice with either KSAC+GLA-SE or L110f+GLA-SE to assess protection against L. major transmitted via its vector Phlebotomus duboscqi.

Methods

Mice receiving the KSAC or L110f vaccines were challenged by needle or L. major-infected sand flies. Weekly disease progression and terminal parasite loads were determined. Immunological responses to KSAC, L110f, or soluble Leishmania antigen (SLA) were assessed throughout vaccination, three and twelve weeks after immunization, and one week post-challenge.

Results

Following sand fly challenge, KSAC-vaccinated mice were protected while L110f-vaccinated animals showed partial protection. Protection correlated with the ability of SLA to induce IFN-γ-producing CD4⁺CD62L^lowCCR7^low effector memory T cells pre- and post-sand fly challenge.

Conclusions

This study demonstrates the protective efficacy of KSAC+GLA-SE against sand fly challenge; the importance of vector-transmitted challenge in evaluating vaccine candidates against Leishmania infection; and the necessity of a rapid potent Th1 response against Leishmania to attain true protection.     

Canine antibody response to Phlebotomus perniciosus bites negatively correlates with the risk of Leishmania infantum transmission

Background

Phlebotomine sand flies are blood-sucking insects that can transmit Leishmania parasites. Hosts bitten by sand flies develop an immune response against sand fly salivary antigens. Specific anti-saliva IgG indicate the exposure to the vector and may also help to estimate the risk of Leishmania spp. transmission. In this study, we examined the canine antibody response against the saliva of Phlebotomus perniciosus, the main vector of Leishmania infantum in the Mediterranean Basin, and characterized salivary antigens of this sand fly species.

Methodology/Principal Findings

Sera of dogs bitten by P. perniciosus under experimental conditions and dogs naturally exposed to sand flies in a L. infantum focus were tested by ELISA for the presence of anti-P. perniciosus antibodies. Antibody levels positively correlated with the number of blood-fed P. perniciosus females. In naturally exposed dogs the increase of specific IgG, IgG1 and IgG2 was observed during sand fly season. Importantly, Leishmania-positive dogs revealed significantly lower anti-P. perniciosus IgG2 compared to Leishmania-negative ones. Major P. perniciosus antigens were identified by western blot and mass spectrometry as yellow proteins, apyrases and antigen 5-related proteins.

Conclusions

Results suggest that monitoring canine antibody response to sand fly saliva in endemic foci could estimate the risk of L. infantum transmission. It may also help to control canine leishmaniasis by evaluating the effectiveness of anti-vector campaigns. Data from the field study where dogs from the Italian focus of L. infantum were naturally exposed to P. perniciosus bites indicates that the levels of anti-P. perniciosus saliva IgG2 negatively correlate with the risk of Leishmania transmission. Thus, specific IgG2 response is suggested as a risk marker of L. infantum transmission for dogs.     

Quantifying the Contribution of Hosts with Different Parasite Concentrations to the Transmission of Visceral Leishmaniasis in Ethiopia

Background

An important factor influencing the transmission dynamics of vector-borne diseases is the contribution of hosts with different parasitemia (no. of parasites per ml of blood) to the infected vector population. Today, estimation of this contribution is often impractical since it relies exclusively on limited-scale xenodiagnostic or artificial feeding experiments (i.e., measuring the proportion of vectors that become infected after feeding on infected blood/host).

Methodology

We developed a novel mechanistic model that facilitates the quantification of the contribution of hosts with different parasitemias to the infection of the vectors from data on the distribution of these parasitemias within the host population. We applied the model to an ample data set of Leishmania donovani carriers, the causative agent of visceral leishmaniasis in Ethiopia.

Results

Calculations facilitated by the model quantified the host parasitemias that are mostly responsible for the infection of vector, the sand fly Phlebotomus orientalis. Our findings indicate that a 3.2% of the most infected people were responsible for the infection of between 53% and 79% (mean – 62%) of the infected sand fly vector population.

Significance

Our modeling framework can easily be extended to facilitate the calculation of the contribution of other host groups (such as different host species, hosts with different ages) to the infected vector population. Identifying the hosts that contribute most towards infection of the vectors is crucial for understanding the transmission dynamics, and planning targeted intervention policy of visceral leishmaniasis as well as other vector borne infectious diseases (e.g., West Nile Fever).     

Large scale systemic control short-circuits pathogen transmission by interrupting the sand rat (Psammomys obesus)-to-sand fly (Phlebotomus papatasi) Leishmania major transmission cycle

Systemic control uses the vertebrate hosts of zoonotic pathogens as “Trojan horses,” killing blood-feeding female vectors and short-circuiting host-to-vector pathogen transmission. Previous studies focused only on the effect of systemic control on vector abundance at small spatial scales. None were conducted at a spatial scale relevant for vector control and none on the effect of systemic control on pathogen transmission rates. We tested the application of systemic control, using Fipronil-impregnated rodent baits, in reducing Leishmania major (Kinetoplastida: Trypanosomatidae; Yakimoff & Schokhor, 1914) infection levels within the vector, Phlebotomus papatasi (Diptera: Psychodidae; Scopoli, 1786) population, at the town-scale. We provided Fipronil-impregnated food-baits to all Psammomys obesus (Mammalia:Muridae; Cretzschmar, 1828), the main L. major reservoir, burrows along the southern perimeter of the town of Yeruham, Israel, and compared sand fly abundance and infection levels with a non-treated control area. We found a significant and substantial treatment effect on L. major infection levels in the female sand fly population. Sand fly abundance was not affected. Our results demonstrate, for the first time, the potential of systemic control in reducing pathogen transmission rates at a large, epidemiologically relevant, spatial scale.     

Miltefosine in the treatment of cutaneous leishmaniasis caused by Leishmania braziliensis in Brazil: a randomized and controlled trial

Background

Cutaneous leishmaniasis (CL) is treated with parenteral drugs for decades with decreasing rate cures. Miltefosine is an oral medication with anti-leishmania activity and may increase the cure rates and improve compliance.

Methodology/Principal Findings

This study is a randomized, open-label, controlled clinical trial aimed to evaluate the efficacy and safety of miltefosine versus pentavalent antimony (Sb^v) in the treatment of patients with CL caused by Leishmania braziliensis in Bahia, Brazil. A total of 90 patients were enrolled in the trial; 60 were assigned to receive miltefosine and 30 to receive Sb^v. Six months after treatment, in the intention-to-treat analyses, the definitive cure rate was 53.3% in the Sb^v group and 75% in the miltefosine group (difference of 21.7%, 95% CI 0.08% to 42.7%, p = 0.04). Miltefosine was more effective than Sb^v in the age group of 13–65 years-old compared to 2–12 years-old group (78.9% versus 45% p = 0.02; 68.2% versus 70% p = 1.0, respectively). The incidence of adverse events was similar in the Sb^v and miltefosine groups (76.7% vs. 78.3%). Vomiting (41.7%), nausea (40%), and abdominal pain (23.3%) were significantly more frequent in the miltefosine group while arthralgias (20.7%), mialgias (20.7%) and fever (23.3%) were significantly more frequent in the Sb^v group.

Conclusions

This study demonstrates that miltefosine therapy is more effective than standard Sb^v and safe for the treatment of CL caused by Leishmania braziliensis in Bahia, Brazil.

Trial Registration

Clinicaltrials.gov Identifier {"type":"clinical-trial","attrs":{"text":"NCT00600548","term_id":"NCT00600548"}}NCT00600548