Discovery of essential kinetoplastid-insect adhesion proteins and their function in Leishmania-sand fly interactions.

Leishmania species, members of the kinetoplastid parasites, cause leishmaniasis, a neglected tropical disease, in millions of people worldwide. Leishmania has a complex life cycle with multiple developmental forms, as it cycles between a sand fly vector and a mammalian host; understanding their life cycle is critical to understanding disease spread. One of the key life cycle stages is the haptomonad form, which attaches to insect tissues through its flagellum. This adhesion, conserved across kinetoplastid parasites, is implicated in having an important function within their life cycles and hence in disease transmission. Here, we discover the kinetoplastid-insect adhesion proteins (KIAPs), which localise in the attached Leishmania flagellum. Deletion of these KIAPs impairs cell adhesion in vitro and prevents Leishmania from colonising the stomodeal valve in the sand fly, without affecting cell growth. Additionally, loss of parasite adhesion in the sand fly results in reduced physiological changes to the fly, with no observable damage of the stomodeal valve and reduced midgut swelling. These results provide important insights into a comprehensive understanding of the Leishmania life cycle, which will be critical for developing transmission-blocking strategies.

Overview and Approaches for Handling of Animal Models of Leishmaniasis.

Leishmaniasis, a disease of global relevance, results from infection with the protozoan parasite, Leishmania, which is transmitted to susceptible hosts through the bite of sand flies. Multiple forms of leishmaniasis may occur, including cutaneous, mucocutaneous, and visceral. Research with animal models remains an important approach to help define basic pathophysi- ologic processes associated with infection and disease. In this regard, mice and hamsters represent the most commonly used models. The severity of leishmaniasis in animal models depends on several factors, including genotype of the host and parasite and the dose and route of administration of the parasite to the host, and severity of outcome may range from subclinical to severe illness. This review provides basic background on leishmaniasis, relevant animal models, the pathophysiology and clinical signs in animals used as models of leishmaniasis, and general approaches to mitigate risk to personnel.

Phlebotomine sand fly distribution and abundance in France: A systematic review.

Global changes in climate are contributing to modified Phlebotomine sand fly presence and activity, and the distribution of the pathogens they transmit (e.g., Leishmania and Phlebovirus), and are leading to their possible extension toward northern France. To predict the evolution of these pathogens and control their spread, it is essential to identify and characterize the presence and abundance of potential vectors. However, there are no recent publications describing sand fly species distribution in France. Consequently, we carried out a systematic review to provide distribution and abundance maps over time, along with a simplified dichotomous key for species in France. The review adhered to PRISMA guidelines, resulting in 172 relevant capture reports from 168 studies out of the 2646 documents retrieved, of which 552 were read and 228 analyzed. Seven species were recorded and categorized into three groups based on their abundance: low abundance species, abundant but little-studied species, and abundant vector species. Sand flies are certainly present throughout France but there is a greater diversity of species in the Mediterranean region. Phlebotomus perniciosus and Ph. ariasi are the most abundant and widely distributed species, playing a role as vectors of Leishmania. Sergentomyia minuta, though very abundant, remains under-studied, highlighting the need for further research. Phlebotomus papatasi, Ph. perfiliewi, Ph. sergenti, and Ph. mascittii are present in low numbers and are less documented, limiting understanding of their potential role as vectors. This work provides the necessary basis for comparison of field data generated in the future.

Title: Répartition et abondance des phlébotomes en France : revue systématique. Abstract: Les changements globaux du climat contribuent à modifier la présence et l'activité des phlébotomes, ainsi que la répartition des pathogènes qu'ils transmettent (par exemple Leishmania et Phlebovirus), et conduisent à leur éventuelle extension vers le nord de la France. Pour prédire l'évolution de ces pathogènes et contrôler leur propagation, il est essentiel d'identifier et de caractériser la présence et l'abondance des vecteurs potentiels. Il n'existe cependant aucune publication récente décrivant la répartition des espèces de phlébotomes en France. Par conséquent, nous avons réalisé une revue systématique pour fournir des cartes de répartition et d'abondance dans le temps, ainsi qu'une clé dichotomique simplifiée pour les espèces françaises. La revue a respecté les lignes directrices PRISMA, aboutissant à 172 rapports de capture pertinents provenant de 168 études sur les 2 646 documents récupérés, dont 552 ont été lus et 228 analysés. Sept espèces ont été recensées et classées en trois groupes en fonction de leur abondance : les espèces de faible abondance, les espèces abondantes mais peu étudiées et les espèces vectrices abondantes. Les phlébotomes sont certes présents partout en France mais on trouve une plus grande diversité d'espèces dans le bassin méditerranéen. Phlebotomus perniciosus et Ph. ariasi sont les espèces les plus abondantes et les plus largement réparties, jouant un rôle de vecteurs de Leishmania. Sergentomyia minuta, bien que très abondant, reste sous-étudié, ce qui souligne la nécessité de recherches plus approfondies. Phlebotomus papatasi, Ph. perfiliewi, Ph. sergenti et Ph. mascittii sont présents en faibles nombres et sont moins documentés, ce qui limite la compréhension de leur rôle potentiel en tant que vecteurs. Ce travail fournit la base nécessaire pour la comparaison des données de terrain générées à l'avenir.

Discriminating motilities: Coordinating IFT with flagellar beating patterns.

Intraflagellar transport has traditionally been studied in immobilized flagella. In this issue, Gray et al. (https://doi.org/10.1083/jcb.202401154) introduced a novel methodology for fast imaging in free-swimming Leishmania, revealing the impacts of flagellum immobilization on intraflagellar transport and its inverse correlation with cell swimming speed.

Aminopyridines in the development of drug candidates against protozoan neglected tropical diseases.

Neglected tropical diseases (NTDs) pose a major threat in tropical zones for impoverished populations. Difficulty of access, adverse effects or low efficacy limit the use of current therapeutic options. Therefore, development of new drugs against NTDs is a necessity. Compounds containing an aminopyridine (AP) moiety are of great interest for the design of new anti-NTD drugs due to their intrinsic properties compared with their closest chemical structures. Currently, over 40 compounds with an AP moiety are on the market, but none is used against NTDs despite active research on APs. The aim of this review is to present the medicinal chemistry work carried out with these scaffolds, against protozoan NTDs: Trypanosoma cruzi, Trypanosoma brucei or Leishmania spp.

[Box: see text].

Unveiling the Enigmatic nature of six neglected Amazonian Leishmania (Viannia) species using the hamster model: Virulence, Histopathology and prospection of LRV1.

American tegumentary leishmaniasis (ATL) is highly endemic in the Amazon basin and occurs in all South American countries, except Chile and Uruguay. Most Brazilian ATL cases are due to Leishmania (Viannia) braziliensis, however other neglected Amazonian species are being increasingly reported. They belong to the subgenus L. (Viannia) and information on suitable models to understand immunopathology are scarce. Here, we explored the use of the golden hamster Mesocricetus auratus and its macrophages as a model for L. (Viannia) species. We also studied the interaction of parasite glycoconjugates (LPGs and GIPLs) in murine macrophages. The following strains were used: L. (V.) braziliensis (MHOM/BR/2001/BA788), L. (V.) guyanensis (MHOM/BR/85/M9945), L. (V.) shawi (MHOM/BR/96/M15789), L. (V.) lindenbergi (MHOM/BR/98/M15733) and L. (V.) naiffi (MDAS/BR/79/M5533). In vivo infections were initiated by injecting parasites into the footpad and were followed up at 20- and 40-days PI. Parasites were mixed with salivary gland extract (SGE) from wild-captured Nyssomyia neivai prior to in vivo infections. Animals were euthanized for histopathological evaluation of the footpads, spleen, and liver. The parasite burden was evaluated in the skin and draining lymph nodes. In vitro infections used resident peritoneal macrophages and THP-1 monocytes infected with all species using a MOI (1:10). For biochemical studies, glycoconjugates (LPGs and GIPLs) were extracted, purified, and biochemically characterized using fluorophore-assisted carbohydrate electrophoresis (FACE). They were functionally evaluated after incubation with macrophages from C57BL/6 mice and knockouts (TLR2-/- and TLR4-/-) for nitric oxide (NO) and cytokine/chemokine production. All species, except L. (V.) guyanensis, failed to generate evident macroscopic lesions 40 days PI. The L. (V.) guyanensis lesions were swollen but did not ulcerate and microscopically were characterized by an intense inflammatory exudate. Despite the fact the other species did not produce visible skin lesions there was no or mild pro-inflammatory infiltration at the inoculation site and parasites survived in the hamster skin/lymph nodes and even visceralized. Although none of the species caused severe disease in the hamster, they differentially infected peritoneal macrophages in vitro. LPGs and GIPLs were able to differentially trigger NO and cytokine production via TLR2/TLR4 and TLR4, respectively. The presence of a sidechain in L. (V.) lainsoni LPG (type II) may be responsible for its higher proinflammatory activity. After Principal Component analyses using all phenotypic features, the clustering of L. (V.) lainsoni was separated from all the other L. (Viannia) species. We conclude that M. auratus was a suitable in vivo model for at least four dermotropic L. (Viannia) species. However, in vitro studies using peritoneal cells are a suitable alternative for understanding interactions of the six L. (Viannia) species used here. LRV1 presence was found in L. (V.) guyanensis and L. (V.) shawi with no apparent correlation with virulence in vitro and in vivo. Finally, parasite glycoconjugates were able to functionally trigger various innate immune responses in murine macrophages via TLRs consistent with their inflammatory profile in vivo.

Veterinary perspectives on the urbanization of leishmaniosis in Morocco.

BACKGROUND: Leishmaniosis caused by Leishmania infantum, L. major and L. tropica is endemic in Morocco. Growing evidence of both human and canine Leishmania infections in urban centres has been reported. Since many forms of the disease are zoonotic, veterinarians play an important role in leishmaniosis control by intervening at the parasite host level. This study aimed to bring together One Health principles to connect canine and feline leishmaniosis epidemiology within urban centres of Morocco (Rabat and Fez) and assess the level of awareness of Moroccan veterinarians about facing this threat. METHODS: A molecular survey was conducted for Leishmania DNA detection in canine (n = 155) and feline (n = 32) whole-blood samples. Three conventional polymerase chain reaction (PCR) protocols were implemented. The first PCR aimed at identifying infected animals by targeting Leishmania spp. kinetoplast minicircle DNA (kDNA). The second and third PCR targeted the Leishmania internal transcribed spacer region (ITS-1) and the Leishmania small subunit ribosomal RNA (SSUrRNA) gene, respectively, aiming at identification of the infecting species after Sanger sequencing-positive amplicons. Total immunoglobulin G (IgG) against Leishmania spp. was evaluated in 125 dogs by enzyme-linked immunosorbent assays (ELISA) using an in-house protocol, including three Leishmania-specific antigens (SPLA, rKDDR and LicTXNPx). Sera from 25 cats were screened for total IgG to Leishmania spp. by an indirect immunofluorescence antibody test (IFAT). An online questionnaire was presented to Moroccan veterinarians addressing their knowledge and practices towards animal leishmaniosis. RESULTS: Overall, 19.4% of the dogs tested positive for Leishmania kDNA and ITS-1 and sequencing revealed infection with L. infantum among PCR-positive dogs. These animals presented a wide range of ELISA seropositivity results (16.7%, 34.9% and 51.6%) according to the tested antigens (rKDDR, SPLA and LicTXNPx, respectively). Use of kDNA-PCR revealed 12.5% cats positive to Leishmania spp. otherwise found to be seronegative by IFAT. CONCLUSIONS: A considerable prevalence of infection was identified in dogs from urban centres of Morocco. Additionally, this is the first report of feline infection with Leishmania spp. in this country and in urban settings. Moroccan veterinarians are aware that animal leishmaniosis is endemic in Morocco, representing a public health threat, and are knowledgeable about canine leishmaniosis diagnosis and treatment.

Sergentomyia khawi: a potential vector for Leishmania and Trypanosoma parasites affecting humans and animals and insecticide resistance status in endemic areas of Songkhla, southern Thailand.

BACKGROUND: Sand flies serve as crucial vectors in various medical and veterinary diseases. Sand fly-borne diseases pose a significant public health burden globally, as the causative agents can infect a diverse range of hosts, leading to severe consequences such as leishmaniasis and sand fly fever. Additionally, the widespread use of insecticides for agricultural purposes and mosquito control is not specifically targeted at sand flies, potentially leading to resistance development. We investigated sand fly species, their potential role as vectors of various parasitic agents, and insecticide resistance in the endemic regions of Natawi and Sadao districts in Songkhla, Thailand. METHODS: Sand flies were collected using CDC light traps. The collected sand flies were then identified to species level using molecular techniques. Subsequent analyses included the detection of pathogens and the identification of pyrethroid resistance mutations within the voltage-sensitive sodium channel (Vgsc) domain IIS6 gene, followed by sequence analysis. RESULTS: The study identified nine sand fly species belonging to the genera Phlebotomus and Sergentomyia. The DNA of Sergentomyia khawi was the only species found to test positive for one sample of Leishmania orientalis in Sadao district. This finding represents the first detection of L. orientalis in Thailand. Moreover, three samples of Leishmania martiniquensis and four samples of Trypanosoma sp. were found in the Natawi district. No I1011M, L1014F/S, V1016G, or F1020S mutations were detected in Vgsc gene. CONCLUSIONS: The results of this study provide valuable information on sand fly species and the continuous circulation of Leishmania spp. and Trypanosoma spp. in Songkhla, southern Thailand. Moreover, the development of geo-spatial information on vectors, parasites, and insecticide resistance in sand flies has the potential to provide well-informed risk assessments and evidence-based guidance for targeted vector control in Thailand. These results can serve as a foundation for integrating the One Health approach, which is crucial for disease control, considering the diverse ecological interactions among human and/or animal reservoir hosts, parasites, and sand fly vectors.

Entomological inferences highlight the risk of Leishmania transmission in the urban area of Porto Velho, Rondônia, Brazil.

Entomological investigations were conducted for the first time in urban forest remnants of Porto Velho, state of Rondônia, Brazil, to explore the transmission dynamics of Leishmania. Sand fly collections were carried out at ten sites, encompassing both canopy and ground strata, from October to December 2021. A total of 1,671 sand flies were collected, representing 42 species within 12 genera. Nyssomyia Antunesi (n = 384) and Psychodopygus davisi (n = 111) were the most abundant species. Molecular analyses targeting the V7V8 region (18S gene) unveiled the presence of sequences 100% identical to Leishmania infantum in females of Bichromomyia flaviscutellata (1), Nyssomyia Antunesi complex (6), Nyssomyia umbratilis (1), Nyssomyia sp. (1), Psychodopygus ayrozai (1), Ps. davisi (3), Psychodopygus paraensis (1), and Sciopemyia sordellii (1). Sequences 100% similar to Trypanosoma minasense were found in two samples of the Nyssomyia Antunesi complex, and two samples of Sc. sordellii presented 100% identity to a Trypanosoma sp. strain, previously identified in this same sand fly in Rondônia. Sequencing of Cytb fragment suggested Homo sapiens, Dasypus novemcinctus and Tamandua tetradactyla as the blood source for distinct sand flies. The identification of sequences similar to L. infantum in sand flies collected in urban forest fragments is noteworthy, correlating with the recent local and regional occurrence of autochthonous cases of human visceral leishmaniasis. However, further studies are imperative to ascertain the presence of hosts/reservoirs and evaluate the risk of L. infantum transmission to humans.

Evaluation of the Leishmania Inositol Phosphorylceramide Synthase as a Drug Target Using a Chemical and Genetic Approach.

The lack of effective vaccines and the development of resistance to the current treatments highlight the urgent need for new anti-leishmanials. Sphingolipid metabolism has been proposed as a promising source of Leishmania-specific targets as these lipids are key structural components of the eukaryotic plasma membrane and are involved in distinct cellular events. Inositol phosphorylceramide (IPC) is the primary sphingolipid in the Leishmania species and is the product of a reaction mediated by IPC synthase (IPCS). The antihistamine clemastine fumarate has been identified as an inhibitor of IPCS in L. major and a potent anti-leishmanial in vivo. Here we sought to further examine the target of this compound in the more tractable species L. mexicana, using an approach combining genomic, proteomic, metabolomic and lipidomic technologies, with molecular and biochemical studies. While the data demonstrated that the response to clemastine fumarate was largely conserved, unexpected disturbances beyond sphingolipid metabolism were identified. Furthermore, while deletion of the gene encoding LmxIPCS had little impact in vitro, it did influence clemastine fumarate efficacy and, importantly, in vivo pathogenicity. Together, these data demonstrate that clemastine does inhibit LmxIPCS and cause associated metabolic disturbances, but its primary target may lie elsewhere.

A breath of fresh air: impact of insect-borne protozoan parasites on the respiratory system.

The protozoan parasites Plasmodium, Leishmania, and Trypanosoma are transmitted by hematophagous insects and cause severe diseases in humans. These infections pose a global threat, particularly in low-resource settings, and are increasingly extending beyond the current endemic regions. Tropism of parasites is crucial for their development, and recent studies have revealed colonization of noncanonical tissues, aiding their survival and immune evasion. Despite receiving limited attention, cumulative evidence discloses the respiratory system as a significant interface for host-pathogen interactions, influencing the course of (co)infection and disease onset. Due to its pathophysiological and clinical implications, we emphasize that further research is needed to better understand the involvement of the respiratory system and its potential to improve prevention, diagnosis, treatment, and interruption of the chain of transmission.

LeishGEM: genome-wide deletion mutant fitness and protein localisations in Leishmania.

LeishGEM is a genome-wide functional annotation community resource for Leishmania mexicana, where deletion mutant growth in vitro and in vivo is measured and protein localisation is determined by endogenous tagging and LOPIT-DC (localisation of organelle proteins by isotope tagging with differential centrifugation) spatial proteomics. Data are being made available pre-publication via http://leishgem.org which allows data-driven identification of the mechanisms for Leishmania parasitism.

Targeting Leishmania Promastigotes and Amastigotes Forms through Amino Acids and Peptides: A Promising Therapeutic Strategy.

Millions of people worldwide are affected by leishmaniasis, caused by the Leishmania parasite. Effective treatment is challenging due to the biological complexity of the parasite, drug toxicity, and increasing resistance to conventional drugs. To combat this disease, the development of specific strategies to target and selectively eliminate the parasite is crucial. This Review highlights the importance of amino acids in the developmental stages of Leishmania as a factor determining whether the infection progresses or is suppressed. It also explores the use of peptides as alternatives in parasite control and the development of novel targeted treatments. While these strategies show promise for more effective and targeted treatment, further studies to address the remaining challenges are imperative.

Prevalence of Leishmania infection in 205 cats from a referral hospital population in Brazil (2021-2022).

Leishmaniases are a group of neglected diseases of significant public health concern, with Brazil being the primary focus of this disease in the Americas. The municipality of Sobral, in the state of Ceará, is a historical focus of visceral leishmaniasis in both humans and dogs, but data on Leishmania spp. infections in cats are limited. Between April 2021 and February 2022, 205 cats from a referral hospital population were sampled and tested for Leishmania spp. by real-time PCR. Eight cats (3.9%; 95% CI: 1.7-7.5%) tested positive. Among these, three (37.5%) displayed clinical signs compatible with feline leishmaniosis. Non-domiciled cats showed significantly higher positivity compared to domiciled ones (Fisher's exact test, P = 0.0124). Considering their potential role as reservoirs of L. infantum, it is crucial to conduct further studies to understand the Leishmania spp. circulating among cats in Sobral and to implement measures for reducing their exposure to phlebotomine sand fly vectors in this important focus of leishmaniases.

Leishmania spp. in equids and their potential vectors in endemic areas of canine leishmaniasis.

Equids may be infected by zoonotic Leishmania spp., including Leishmania infantum, in regions where canine leishmaniasis (CanL) is endemic, and Leishmania martiniquensis, which has been reported in horses from Central Europe. This study was designed to evaluate the occurrence of both Leishmania spp. among equids living in CanL endemic areas of Italy, as well as to identify dipteran vectors from the same habitats. From March to October 2023, blood, serum and tissue samples from skin lesions were collected from equids (n = 98; n = 56 donkeys and n = 42 horses) living in Italy, as well as sand flies and biting midges. Blood samples (n = 98) and skin lesions (n = 56) were tested for Leishmania spp. by conventional and real time PCRs and sera were tested by immunofluorescence antibody tests (IFAT) for both L. infantum and L. martiniquensis. Insects were morphologically identified, and female specimens (n = 268 sand flies, n = 7 biting midges) analyzed for Leishmania DNA, as well as engorged sand flies (n = 16) for blood-meal detection. Two animals with skin lesions (i.e., one donkey and one horse) scored positive for Leishmania spp. DNA, and 19 animals (i.e., 19.4%; n = 13 donkeys and n = 6 horses) were seropositive for L. infantum, with five of them also for L. martiniquensis. Most seropositive animals had no dermatological lesions (i.e., 68.4%) while both animals molecularly positive for Leishmania spp. scored seronegative. Of the 356 sand flies collected, 12 females (i.e., n = 8 Sergentomyia minuta; n = 3 Phlebotomus perniciosus, n = 1 Phlebotomus perfiliewi) were positive for Leishmania spp. DNA, and one out of seven biting midges collected was DNA-positive for L. infantum. Moreover, engorged sand flies scored positive for human and equine DNA. Data suggest that equids living in CanL endemic areas are exposed to Leishmania spp., but their role in the circulation of the parasite needs further investigations.

In vitro evaluation against Leishmania amazonensis and Leishmania chagasi of medicinal plant species of interest to the Unified Health System.

Leishmaniasis is a disease of public health relevance that demands new therapeutic alternatives due to the toxicity of conventional treatments. In this study, 27 plants of interest to the Unified Health System (SUS) were evaluated for cytotoxicity in macrophages, leishmanicidal activity and production of nitric oxide (NO). None of the species demonstrated cytotoxicity to macrophages (CC50 >100 µg/mL). Extracts from Chenopodium ambrosioides, Equisetum arvense, Maytenus ilicifolia showed greater efficacy in inducing the death of Leishmania amazonensis amastigotes with IC50 of 68.4, 82.3, 75.7 µg/mL, respectively. The species Cynara scolymus, Punica granatum and Passiflora alata were the most effective in inducing an increase in the indirect concentration of NO (41.31, 29.30 and 28.86 µM, respectively) in cultures of macrophages infected with L. amazonensis. Furthermore, Punica granatum was also the most effective species in inducing an increase in NO in macrophages infected by Leishmania chagasi (19.90 µM). The results obtained so far support the continuation of studies, with the possibility of developing safer and more effective treatments for leishmaniasis, using natural products. The identification of plants that stimulate the production of NO in macrophages infected by Leishmania opens doors for more detailed investigations of the mechanism of action of these natural products.

Synthesis, biological evaluation and mechanism of action of benzothiazole derivatives with aromatic hydrazone moiety, a new class of antileishmanial compounds.

Leishmaniasis is a disease caused by protozoa Leishmania spp., considered as a significant and urgent public health problem mainly in developing countries. In the absence of an effective vaccine, the treatment of infected people is one of the most commonly prophylactic measures used to control this disease. However, the therapeutic arsenal is reduced to a few drugs, with serious side effects and variability in efficacy. Attempting to this problem, in this work, a series of benzothiazole derivatives was synthetized and assayed against promastigotes and intracellular amastigotes of L. amazonensis, as well as the toxicity on macrophages. In addition, studies about the mechanism of action were also performed. Among the synthesized molecules, the substitution at position 4 of the aromatic ring appears to be critical for activity. The best compound exhibited IC50 values of 28.86 and 7.70 µM, against promastigotes and amastigotes of L. amazonensis, respectively, being more active than miltefosine, used as reference drug. The in silico analysis of physicochemical and pharmacokinetic (ADMET) properties of this compound suggested a good profile of oral bioavailability and safety. In conclusion, the strategy of using benzothiazole nucleous in the search for new antileishmanial agents was advantageous and preliminar data provide information about the mechanism of action as well as in silico parameters suggest a good profile for preclinical studies.

Prevalence and transmission of the most relevant zoonotic and vector-borne pathogens in the Yucatan peninsula: A review.

BACKGROUND: Habitat modification and land use changes impact ecological interactions and alter the relationships between humans and nature. Mexico has experienced significant landscape modifications at the local and regional scales, with negative effects on forest cover and biological biodiversity, especially in the Yucatan peninsula in southeastern Mexico. Given the close relationship between landscape modification and the transmission of zoonotic and vector-borne diseases, it is essential to develop criteria for identifying priority zoonoses in the south of the country. METHODOLOGY/PRINCIPAL FINDINGS: We reviewed 165 published studies on zoonotic and vector-borne diseases in the region (2015-2024). We identified the most frequent vectors, reservoirs, and hosts, the most prevalent infections, and the factors associated with transmission risk and the anthropogenic landscape modification in urban, rural, ecotone, and sylvatic habitats. The most relevant pathogens of zoonotic risk included Trypanosoma cruzi, arboviruses, Leishmania, Rickettsia, Leptospira, and Toxoplasma gondii. Trypanosoma cruzi was the vector-borne agent with the largest number of infected vertebrate species across habitats, while Leishmania and arboviruses were the ones that affected the greatest number of people. Dogs, cats, backyard animals, and their hematophagous ectoparasites are the most likely species maintaining the transmission cycles in human settlements, while rodents, opossums, bats, and other synanthropic animals facilitate connection and transmission cycles between forested habitats with human-modified landscapes. Pathogens displayed different prevalences between the landscapes, T. cruzi, arbovirus, and Leptospira infections were the most prevalent in urban and rural settlements, whereas Leishmania and Rickettsia had similar prevalence across habitats, likely due to the diversity and abundance of the infected vectors involved. The prevalence of T. gondii and Leptospira spp. may reflect poor hygiene conditions. Additionally, results suggest that prevalence of zoonotic and vector-borne diseases is higher in deforested areas and agricultural aggregates, and in sites with precarious health and infrastructure services. CONCLUSIONS: Some hosts, vectors, and transmission trends of zoonotic and vector-borne diseases in the YP are well known but others remain poorly recognized. It is imperative to reinforce practices aimed at increasing the knowledge, monitoring, prevention, and control of these diseases at the regional level. We also emphasize the need to perform studies on a larger spatio-temporal scale under the socio-ecosystem perspective, to better elucidate the interactions between pathogens, hosts, vectors, environment, and sociocultural and economic aspects in this and many other tropical regions.

Cutaneous leishmaniasis in sub-Saharan Africa: a systematic review of Leishmania species, vectors and reservoirs.

BACKGROUND: Cutaneous leishmaniasis (CL) is understudied in sub-Saharan Africa. The epidemiology of CL is determined by the species involved in its transmission. Our objectives were to systematically review available data on the species of Leishmania, along with vectors and reservoirs involved in the occurrence of human cases of CL in sub-Saharan Africa, and to discuss implications for case management and future research. METHODS: We systematically searched PubMed, Scopus, Cochrane and African Index Medicus. There was no restriction on language or date of publication. The review was conducted according to PRISMA guidelines and was registered on PROSPERO (CRD42022384157). RESULTS: In total, 188 published studies and 37 reports from the grey literature were included. An upward trend was observed, with 45.7% of studies published after 2010. East Africa (55.1%) represented a much greater number of publications than West Africa (33.3%). In East Africa, the identification of reservoirs for Leishmania tropica remains unclear. This species also represents a therapeutic challenge, as it is often resistant to meglumine antimoniate. In Sudan, the presence of hybrids between Leishmania donovani and strictly cutaneous species could lead to important epidemiological changes. In Ghana, the emergence of CL in the recent past could involve rare species belonging to the Leishmania subgenus Mundinia. The area of transmission of Leishmania major could expand beyond the Sahelian zone, with scattered reports in forested areas. While the L. major-Phlebotomus duboscqi-rodent complex may not be the only cycle in the dry areas of West Africa, the role of dogs as a potential reservoir for Leishmania species with cutaneous tropism in this subregion should be clarified. Meglumine antimoniate was the most frequently reported treatment, but physical methods and systemic agents such as ketoconazole and metronidazole were also used empirically to treat L. major infections. CONCLUSIONS: Though the number of studies on the topic has increased recently, there is an important need for intersectional research to further decipher the Leishmania species involved in human cases of CL as well as the corresponding vectors and reservoirs, and environmental factors that impact transmission dynamics. The development of molecular biology in sub-Saharan Africa could help in leveraging diagnostic and research capacities and improving the management of human cases through personalized treatment strategies.

American Cutaneous Leishmaniasis: Imported cases in Berlin 2000-2023.

BACKGROUND: American Cutaneous Leishmaniasis (ACL) shows variable response to therapy, but data on species-specific treatment efficacy is scarce. We describe the clinical characteristics and outcome of patients with ACL imported to a tertiary centre in Germany and determine whether species-specific therapy according to the 2014 "LeishMan" group recommendations is associated with cure. METHODS: A retrospective chart review was conducted at the Charité Institute of International Health in Berlin. We analysed data on PCR-confirmed ACL cases collected between 2000 and 2023. Systemic therapy included liposomal amphotericin B, miltefosine, pentavalent antimony, ketoconazole or itraconazole. Localized therapy included perilesional pentavalent antimony or paromomycin ointment. Cure was defined as re-epithelialization of ulcers or disappearance of papular-nodular lesions after 3 months of treatment. Logistic regression models were used to quantify the effect of species-specific systemic therapy on the outcome. RESULTS: 75 cases were analysed. Most patients were male (62%), median age was 35 years, no patient had a history of immunosuppression. The most common reason for travel was tourism (60%), the most common destination was Costa Rica (28%), the median duration of illness was 8 weeks, and most patients presented with ulcers (87%). Lesions were complex in 43%. The most common Leishmania (L.) species was L. braziliensis (28%), followed by L. panamensis (21%). 51/73 (70%) patients were cured after initial therapy and 17/21 (81%) after secondary therapy. Cure after systemic therapy was more frequent when species-specific treatment recommendations were followed (33/45; 73%), compared to when not followed, (6/17; 35%, P = 0.008). This association was independent of age, sex, previous therapy, complex lesions, and Leishmania species (adjusted OR, 5.06; 95% CI, 1.22-24.16). CONCLUSIONS: ACL is a rare, imported disease in Germany. Complex lesions were common, challenging successful therapy. This study highlights the importance of identifying the parasite species and suggests that a species-specific approach to treatment leads to better outcomes.