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Concept: Leishmania

171

Patients with New World cutaneous leishmaniasis (NWCL) caused by Leishmania Viannia are treated with parenteral sodium stibogluconate (SbV) to reduce the risk of development of mucocutanous leishmaniasis. Our centre manages patients with NWCL on an outpatient-basis. This study was conducted to assess the safety and efficacy of this approach.

Concepts: Leishmaniasis, Visceral leishmaniasis, Cutaneous leishmaniasis, Leishmania, Sodium stibogluconate, Leishmania major, Pentavalent antimonial

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Abstract. Visceral leishmaniasis was first reported in Bhutan in 2006. We conducted studies of the parasite, possible vectors and reservoirs, and leishmanin skin test and risk factor surveys in three villages. Nineteen cases were reported from seven districts. Parasite typing yielded two novel microsatellite sequences, both related to Indian L. donovani. In one case village, 40 (18.5%) of 216 participants had positive leishmanin skin test results, compared with 3 (4.2%) of 72 in the other case village and 0 of 108 in the control village. Positive results were strongly associated with the village and increasing age. None of the tested dogs were infected. Eighteen sand flies were collected, 13 Phlebotomus species and 5 Sergentomyia species; polymerase chain reaction for leishmanial DNA was negative. This assessment suggests that endemic visceral leishmaniasis transmission has occurred in diverse locations in Bhutan. Surveillance, case investigations, and further parasite, vector, and reservoir studies are needed. The potential protective impact of bed nets should be evaluated.

Concepts: DNA, Polymerase chain reaction, DNA polymerase, Leishmaniasis, Leishmania, Thermus aquaticus, Phlebotominae, Canine leishmaniasis

169

Abstract. The occurrence of American cutaneous leishmaniasis (ACL) in areas modified by humans indicates that phlebotomine sand fly vectors breed close to human habitations. Potential peridomiciliary breeding sites of phlebotomines were sampled in an area of transmission of Leishmania (Viannia) braziliensis in Southeastern Brazil. Three concentric circles rounding houses and domestic animal shelters, with radii of 20, 40, and 60 m, defined the area to be monitored using adult emergence traps. Of the 67 phlebotomines collected, Lutzomyia intermedia comprised 71.6%; Lutzomyia schreiberi, 20.9%; and Lutzomyia migonei, 4.5%. The predominance of L. intermedia, the main species suspected of transmitting L. (V.) braziliensis in Southeastern Brazil, indicates its participation in the domiciliary transmission of ACL, providing evidence that the domiciliary ACL transmission cycle might be maintained by phlebotomines that breed close to human habitations. This finding might also help in planning measures that would make the peridomiciliary environment less favorable for phlebotomine breeding sites.

Concepts: Leishmaniasis, Cutaneous leishmaniasis, Leishmania, Flies, Fly, Phlebotominae, Phlebotomus, Lutzomyia

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Introduction: Leishmaniasis is a parasitic disease transmitted by phlebotomine sandflies. Between 700,000 and 1.2 million cases of cutaneous leishmaniasis and between 200,000 and 400,000 cases of visceral leishmaniasis (VL), which is fatal if left untreated, occur annually worldwide. Liposomal amphotericin B (LAMB), alone or in combination with other drugs, has been extensively studied as VL treatment, but data on routine field use are limited, and several challenges to patients' access to this life-saving drug remain. Areas covered: This article provides a review of clinical studies on LAMB for VL and other forms of leishmaniasis. The current development of generic versions of LAMB and related challenges are also discussed. Expert opinion: LAMB proved to be highly efficacious and safe in over 8000 VL patients treated by MÉdecins Sans Frontières in South Asia, and its use was feasible even at primary healthcare level. Despite requiring higher doses, LAMB is the drug of choice to treat vulnerable groups (e.g., pregnant or HIV positive) and relapsing VL patients in East Africa. LAMB should be included in national VL guidelines and registered in all VL endemic countries. Its cost should be further reduced and regulatory pathways to prove bioequivalence for generic LAMB products should be implemented.

Concepts: Illness, Amphotericin B, Leishmaniasis, Visceral leishmaniasis, Generic drug, Cutaneous leishmaniasis, Leishmania, Parasitic diseases

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BACKGROUND: Canine Visceral Leishmaniasis (CVL) is a zoonotic disease caused by Leishmania infantum, transmitted by the bite of Lutzomyia longipalpis sand flies. Dogs are the main domestic reservoir of the parasite. The establishment of an experimental model that partially reproduces natural infection in dogs is very important to test vaccine candidates, mainly regarding those that use salivary proteins from the vector and new therapeutical approaches. METHODOLOGYPRINCIPAL FINDINGS: In this report, we describe an experimental infection in dogs, using intradermal injection of Leishmania infantum plus salivary gland homogenate (SGH) of Lutzomyia longipalpis. Thirty-five dogs were infected with 1×10(7) parasites combined with five pairs of Lutzomyia longipalpis salivary glands and followed for 450 days after infection and clinical, immunological and parasitological parameters were evaluated. Two hundred and ten days after infection we observed that 31,4% of dogs did not display detectable levels of anti-Leishmania antibodies but all presented different numbers of parasites in the lymph nodes. Animals with a positive xenodiagnosis had at least 3,35×10(5) parasites in their lymph nodes. An increase of IFN-γ and IL-10 levels was detected during infection. Twenty two percent of dogs developed symptoms of CVL during infection. CONCLUSION: The infection model described here shows some degree of similarity when compared with naturally infected dogs opening new perspectives for the study of CVL using an experimental model that employs the combination of parasites and sand fly saliva both present during natural transmission.

Concepts: Immune system, Saliva, Leishmaniasis, Leishmania, Glands, Salivary gland, Zoonosis, Phlebotominae

148

Infection with Leishmania donovani is typically asymptomatic, but a significant number of individuals may progress to visceral leishmaniasis (VL), a deadly disease that threatens 200 million people in endemic areas. While diagnosis of acute VL has been simplified by the use of cost-effective confirmatory serological tests, similar standardized tools are not widely available for detecting asymptomatic infection which can be 4-20 times more prevalent than active disease. A simple and accurate serological test capable of detecting asymptomatic L. donovani infection will be useful for surveillance programs targeting VL control and elimination. To address this unmet need, we evaluated recombinant antigens for their ability to detect serum antibodies in 104 asymptomatic L. donovani infected individuals (qualified as positive for L. donovani-specific antibodies by direct agglutination test; DAT) from the VL hyperendemic Mymensingh district of Bangladesh. The novel proteins rKR95 and rTR18 possessed the greatest potential and detected 69% of DAT positive individuals, with rKR95 being more robust in reactivity. Agreement in results with individuals with high DAT responses, who are more likely to progress to VL disease, was 74%. When considered along with rK39, a gold standard antigen used to confirm clinical diagnosis of VL but which is now becoming widely used for surveillance, rKR95 and rTR18 conferred a sensitivity of 84% based on a theoretical combined estimate. Our data indicate that incorporating rKR95 and rTR18 with rK39 in serological tests amenable to rapid or high-throughput screening could enable simple and accurate detection of asymptomatic infection. Such tests will be important tools to measure L. donovani infection rates, a primary goal in surveillance and a critical measurement with which to assess elimination programs.

Concepts: Immune system, Antibody, Epidemiology, Leishmaniasis, Visceral leishmaniasis, Leishmania, Serology, Direct agglutination test

28

New World cutaneous leishmaniasis is mostly acquired in the Amazon Basin of Bolivia where L viannia (V) braziliensis is endemic. Treatment with systemic pentavalent antimonial compounds has been shown to be effective in achieving clinical cure in only 75% of cases.

Concepts: Amphotericin B, Leishmaniasis, Visceral leishmaniasis, Cutaneous leishmaniasis, Leishmania, Amazon River, Sodium stibogluconate, Pentavalent antimonial

28

Leishmania siamensis was firstly described as a causative agent of autochthonous visceral leishmaniasis in southern provinces of Thailand since 2008. The spread of leishmaniasis depends on the distribution of the vectors and reservoir hosts. Unfortunately, little is known about these vital factors. The objective of this study was to identify the distribution of sandfly species, their density, and their habitats in the affected areas of leishmaniasis, southern Thailand. A cross-sectional survey of sandflies was conducted in three provinces of southern Thailand where leishmaniasis cases were previously reported. The collection of sandflies was performed using CDC light traps for four consecutive months, from March to June 2009. A total of 2,698 sandflies were collected in the affected areas. Among 1,451 female sandflies, six species of genus Sergentomyia were identified, i.e., Sergentomyia gemmea, Sergentomyia iyengari, Sergentomyia barraudi, Sergentomyia indica, Sergentomyia silvatica, and Sergentomyia perturbans. S. gemmea (81.4 %) was the most predominant species in all areas. In addition, one species of the genus Phlebotomus, Phlebotomus argentipes, a known vector of leishmaniasis was also detected. The distribution of sandfly species in these leishmaniasis-affected areas was different from the previous studies in other areas of Thailand. Further studies are needed to proof whether these sandflies can be the natural vectors of leishmaniasis.

Concepts: Leishmaniasis, Visceral leishmaniasis, Leishmania, Canine leishmaniasis, Phlebotomus, Lutzomyia, Surat Thani Province, Yala Province

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SUMMARY Current treatments for different clinical forms of leishmaniasis are unsatisfactory, highly toxic and associated with increasing failure rates resulting from the emergence of resistant parasites. Leishmania (Viannia) braziliensis is the main aetiological agent of different clinical forms of American tegumentary leishmaniasis, including the mucosal form for which treatment has high failure rates. The aim of this work was to investigate the activity of the Morita-Baylis-Hillman adduct, methyl 2-{2-[hydroxy(2-nitrophenyl)methyl])acryloyloxy} benzoate in vitro against isolates of L. (V.) braziliensis obtained from patients with different clinical manifestations of tegumentary leishmaniasis: localized cutaneous leishmaniasis, mucosal leishmaniasis and disseminated cutaneous leishmaniasis. The adduct effectively inhibited the growth of promastigotes of the different isolates of L. (V.) braziliensis (IC50 ⩽ 7·77 μg/ml), as well as reduced the infection rate of macrophages infected with these parasites (EC50 ⩽ 1·37 μg/ml). It is remarkable to state that the adduct was more effective against intracellular amastigotes (P ⩽ 0·0045). The anti-amastigote activity correlated with an immunomodulatory effect, since the adduct was able to decrease the production of IL-6 and IL-10 by the infected macrophages. However, its effect was independent of nitric oxide production. This work demonstrates the anti-leishmanial activity of methyl 2-{2-[hydroxy(2-nitrophenyl)methyl])acryloyloxy} benzoate and suggests its potential in the treatment of human infections caused by L. (V.) braziliensis.

Concepts: Immune system, Infection, Effectiveness, Transmission and infection of H5N1, Nitric oxide, Leishmaniasis, Cutaneous leishmaniasis, Leishmania