Investigation of a new focus of Cutaneous Leishmaniasis in Ghana

Leishmaniasis is a disease of significant public health importance, which burdens a number of countries around the world, particularly in the tropics and subtropics. An outbreak of suspected cutaneous leishmaniasis (CL) has been witnessed in the Ho district of the Volta region in the south-eastern part of Ghana since 1999, where chronic ulcers typical of CL are being diagnosed. In this part of Ghana leishmaniasis has remained endemic to date. To add to the improvement of the level of understanding of the diseases in Ghana; the identity of the parasite, vector incrimination, non-invasive and field friendly diagnosis, and compound susceptibility tests were investigated. Patients presenting with cutaneous lesions suggestive of CL were selected where skin aspirates were collected from the sites of active lesion(s). Portions of the aspirates were cultured in M199 medium and DNA extracted from the promastigotes generated, while portions of the aspirates were inoculated onto FTA cards. PCR and PCR-RFLP were directly performed on the isolated DNA and the FTA cards. The pattern of bands produced from the patient samples were a complete deviation from DNAs of all the positive controls of Leishmania species. The sequenced PCR products and the further phylogenetic analysis revealed close relatedness to Leishmania enriettii species. The Leishmania species (GH5) responsible for the CL cases in that part of Ghana were successfully isolated into culture for the first time and proved to be distinct from the known species but closely related to non-pathogenic Leishmania enriettii. The transmission and the scanning electron micrograph evidence of the parasite confirmed their Leishmania identity. A peroxidoxin-based simple field friendly antigen detection test device was found diagnostically sensitive to Ghana species (GH5) and the other species of Leishmania used as controls in the diagnostic investigation. In the compound susceptibility test, the species isolated from Ghana (GH5) was found to be relatively resistant to cryptolepine, at concentrations to which the control species Leishmania mexicana was susceptible

First isolation of Leishmania from Northern Thailand:case report, identification as Leishmania martiniquensis and phylogenetic position within the Leishmania enriettii complex

Since 1996, there have been several case reports of autochthonous visceral leishmaniasis in Thailand. Here we report a case in a 52-year-old Thai male from northern Thailand, who presented with subacute fever, huge splenomegaly and pancytopenia. Bone marrow aspiration revealed numerous amastigotes within macrophages. Isolation of Leishmania LSCM1 into culture and DNA sequence analysis (ribosomal RNA ITS-1 and large subunit of RNA polymerase II) revealed the parasites to be members of the Leishmania enriettii complex, and apparently identical to L. martiniquensis previously reported from the Caribbean island of Martinique. This is the first report of visceral leishmaniasis caused by L. martiniquensis from the region. Moreover, the majority of parasites previously identified as "L. siamensis" also appear to be L. martiniquensis

First isolation of a new species of Leishmania responsible for human cutaneous leishmaniasis in Ghana and classification in the Leishmania enriettii complex

An active case detection approach with PCR diagnosis was used in the Ho District of the Volta Region, Ghana that identified individuals with active cutaneous leishmaniasis. Three isolates were successfully cultured and DNA sequences from these were analysed (ribosomal RNA internal transcribed spacer 1; ribosomal protein L23a intergenic spacer; RNA polymerase II large subunit), showing them to be Leishmania, identical to each other but different from all other known Leishmania spp. Phylogenetic analysis showed the parasites to be new members of the Leishmania enriettii complex, which is emerging as a possible new subgenus of Leishmania parasites containing human pathogens

An outbreak of suspected cutaneous leishmaniasis in Ghana: lessons learnt and preparation for future outbreaks

Human cutaneous leishmaniasis (CL) has previously been reported in West Africa, but more recently, sporadic reports of CL have increased. Leishmania major has been identified from Mauritania, Senegal, Mali, and Burkina Faso. Three zymodemes (MON-26, MON-117, and MON-74, the most frequent) have been found. The geographic range of leishmaniasis is limited by the sand fly vector, its feeding preferences, and its capacity to support internal development of specific species of Leishmania. The risk of acquiring CL has been reported to increase considerably with human activity and epidemics of CL have been associated with deforestation, road construction, wars, or other activities where humans intrude the habitat of the vector. In the Ho Municipality in the Volta Region of Ghana, a localised outbreak of skin ulcers, possibly CL, was noted in 2003 without any such documented activity. This outbreak was consistent with CL as evidenced using various methods including parasite identification, albeit, in a small number of patients with ulcers

The therapeutic landscape of HIV-1 via genome editing

Abstract Current treatment for HIV-1 largely relies on chemotherapy through the administration of antiretroviral drugs. While the search for anti-HIV-1 vaccine remain elusive, the use of highly active antiretroviral therapies (HAART) have been far-reaching and has changed HIV-1 into a manageable chronic infection. There is compelling evidence, including several side-effects of ARTs, suggesting that eradication of HIV-1 cannot depend solely on antiretrovirals. Gene therapy, an expanding treatment strategy, using RNA interference (RNAi) and programmable nucleases such as meganuclease, zinc finger nuclease (ZFN), transcription activator-like effector nuclease (TALEN), and clustered regularly interspaced short palindromic repeats/CRISPR-associated proteins (CRISPR–Cas9) are transforming the therapeutic landscape of HIV-1. TALENS and ZFNS are structurally similar modular systems, which consist of a FokI endonuclease fused to custom-designed effector proteins but have been largely limited, particularly ZFNs, due to their complexity and cost of protein engineering. However, the newly developed CRISPR–Cas9 system, consists of a single guide RNA (sgRNA), which directs a Cas9 endonuclease to complementary target sites, and serves as a superior alternative to the previous protein-based systems. The techniques have been successfully applied to the development of better HIV-1 models, generation of protective mutations in endogenous/host cells, disruption of HIV-1 genomes and even reactivating latent viruses for better detection and clearance by host immune response. Here, we focus on gene editing-based HIV-1 treatment and research in addition to providing  perspectives for refining these techniques

Effect of high fat diet on experimental CD outcomes.

Effect of high fat diet on experimental CD outcomes.</p

Representative metabolism-modulating strategies tested in CD mouse models.

Representative metabolism-modulating strategies tested in CD mouse models.</p

The structural diversity of metabolites: Representative metabolite structures, as discussed in the text.

The depicted molecules span a range of chemical classes, including amino acids (arginine), nucleosides (adenosine), coenzymes (tetrahydrobiopterin), and fatty acids (TG). Figure created in ChemDraw 20.1.</p

Identification of Sand Flies (Diptera: Psychodidae) Collected from Cutaneous Leishmaniasis Endemic Focus in the Ho Municipality, Ghana

Leishmaniasis, is a vector-borne disease transmitted to humans through the bite of infected female sand flies. Active and continuous monitoring of the sand fly is an important aspect of disease control. Thus, the correct identification of its vectors is paramount in this regard. Objective: The study was conducted to morphologically and molecularly identify female sand fly species in a cutaneous leishmaniasis endemic focus collected in three villages in the Ho Municipality of the Volta region. CDC light traps and sticky paper traps was used for the collection of the sand flies. The morphologically identified sand flies was molecularly confirmed by running PCR with the mitochondrial cytochrome c oxidase gene subunit I (COI) primers and DNA sequenced. A total of 537 sand flies was collected, made up of 363 females and 174 males.  Eleven different species of sand flies was morphologically identified – one Phlebotomus species and ten Sergentomyia species. The PCR amplified products showed bands of molecular weights 658 base pairs for the primers. The molecular identification using the 658-bp fragment of the (COI) gene was congruent with the morphological identification

Conceptual overview of metabolic interactions between <i>T</i>. <i>cruzi</i>, the microbiome, and the mammalian host.

Curved arrows indicate interactions. Diet, T. cruzi, the microbiome and immune responses all reshape host metabolic pathways. Some of these changes can impair parasite growth or promote antiparasitic immune responses, while other changes are maladaptive and lead to impaired organ function and disease symptoms. Figure created with BioRender.com.</p