Pharmacokinetics and Pharmacodynamics of Fosravuconazole, Itraconazole and Hydroxyitraconazole in Sudanese Patients With Eumycetoma.

Background: The first clinical trial on eumycetoma was recently conducted in Sudan, comparing oral fosravuconazole, prodrug of active ravuconazole, with the standard-of-care oral itraconazole. Building on this trial, the present study aimed to characterize the pharmacokinetics-pharmacodynamics (PK-PD) of ravuconazole, itraconazole and hydroxyitraconazole in patients with eumycetoma and guide selection of either a 200 mg or 300 mg dose of fosravuconazole.

Methods: Nonlinear mixed-effects modeling was used to develop population PK models in 52 patients receiving three daily loading doses followed by weekly fosravuconazole (200 mg or 300 mg) or twice daily itraconazole (total 400 mg), both over 12 months.

Unsupervised machine learning identifies biomarkers of disease progression in post-kala-azar dermal leishmaniasis in Sudan.

Background: Post-kala-azar dermal leishmaniasis (PKDL) appears as a rash in some individuals who have recovered from visceral leishmaniasis caused by Leishmania donovani. Today, basic knowledge of this neglected disease and how to predict its progression remain largely unknown.

Methods And Findings: This study addresses the use of several biochemical, haematological and immunological variables, independently or through unsupervised machine learning (ML), to predict PKDL progression risk.

Two dose levels of once-weekly fosravuconazole versus daily itraconazole in combination with surgery in patients with eumycetoma in Sudan: a randomised, double-blind, phase 2, proof-of-concept superiority trial.

Background: Eumycetoma is an implantation mycosis characterised by a large subcutaneous mass in the extremities commonly caused by the fungus Madurella mycetomatis. Despite the long duration of treatment, commonly a minimum of 12 months, treatment failure is frequent and can lead to amputation. We aimed to compare the efficacy of two doses of fosravuconazole, a synthetic antifungal designed for use in onychomycosis and repurposed for mycetoma, with standard-of-care itraconazole, both in combination with surgery.

Differences in the Cellular Immune Response during and after Treatment of Sudanese Patients with Post-kala-azar Dermal Leishmaniasis, and Possible Implications for Outcome.

Background: The host cellular immune response associated with two treatments for post-kala-azar dermal leishmaniasis (PKDL) - paromomycin plus miltefosine (Arm 1), and liposomal amphotericin B plus miltefosine (Arm 2) - was examined in Sudanese patients before treatment (D0), at the end of treatment (D42), and during the post-treatment period (D180).

Methods: Whole blood samples were stimulated with soluble Leishmania antigen for 24 h (whole blood assay [WBA]) and the concentrations of Th1/Th2/Th17-associated cytokines, IP-10, PDL-1 and granzyme B were determined.

Results: The Arm 1 treatment (98.

Safety and efficacy of paromomycin/miltefosine/liposomal amphotericin B combinations for the treatment of post-kala-azar dermal leishmaniasis in Sudan: A phase II, open label, randomized, parallel arm study.

Background: Treatment for post-kala-azar dermal leishmaniasis (PKDL) in Sudan is currently recommended only for patients with persistent or severe disease, mainly because of the limitations of current therapies, namely toxicity and long hospitalization. We assessed the safety and efficacy of miltefosine combined with paromomycin and liposomal amphotericin B (LAmB) for the treatment of PKDL in Sudan.

Methodology/principal Findings: An open-label, phase II, randomized, parallel-arm, non-comparative trial was conducted in patients with persistent (stable or progressive disease for ≥ 6 months) or grade 3 PKDL, aged 6 to ≤ 60 years in Sudan.

Delayed cerebellar ataxia induced by malaria: A rare complication.

Key Clinical Message: In endemic areas, malaria-induced cerebellar ataxia should be suspected in patients presenting with neurological disorders including slurred speech, tremors, and a sense of imbalance and dizziness while walking. Healthcare providers should be aware to properly investigate and early detect and manage infections associated with the development of cerebellar ataxia to improve the case management and clinical outcome cost-effectively.

Abstract: Here, we report the clinical manifestations, investigations, and outcomes of a patient developed delayed cerebellar ataxia following a malaria infection: an unusual complication of the disease.

Guillain-Barre syndrome associated with COVID-19 infection: A case series.

In this communication, we reported a series of six patients presented with Guillain-Barré syndrome that associated with COVID-19 infection, which was confirmed with RT-PCR. Here we discuss the laboratory investigation and case management, as well as clinical presentation and outcome of each case. The current report demonstrated the first case series of COVID-19-associated GBS-cases in Sudan.

A holistic approach to the mycetoma management.

Mycetoma, one of the badly neglected tropical diseases, it is a localised chronic granulomatous inflammatory disease characterised by painless subcutaneous mass and formation of multiple sinuses that produce purulent discharge and grains. If untreated early and appropriately, it usually spread to affect the deep structures and bone resulting in massive damage, deformities and disabilities. It can also spread via the lymphatics and blood leading to distant secondary satellites associated with high morbidity and mortality.

Prevalence of latent tuberculosis infection in Sudan: a case-control study comparing interferon-γ release assay and tuberculin skin test.

Background: Most people exposed to M. tuberculosis show no evidence of clinical disease. Five to 10% of individuals with latent infection progress to develop overt disease during their life time.

Post-Kala-Azar Dermal Leishmaniasis: A Paradigm of Paradoxical Immune Reconstitution Syndrome in Non-HIV/AIDS Patients.

Visceral leishmaniasis (VL) is a parasitic disease characterized by immune suppression. Successful treatment is usually followed by immune reconstitution and a dermatosis called post-Kala-azar dermal leishmaniasis (PKDL). Recently, PKDL was described as one of the immune reconstitution syndromes (IRISs) in HIV/VL patients on HAART.

Misdiagnosis and mistreatment of post-kala-azar dermal leishmaniasis.

Post-kala-azar dermal leishmaniasis (PKDL) is a known complication of visceral leishmaniasis (VL) caused by L. donovani. It is rare in VL caused by L.

Immunological stimulation for the treatment of leishmaniasis: a modality worthy of serious consideration.

Instead of relying on drugs to reduce the parasite burden of leishmaniasis, and waiting for the effector immune response to develop in time to control the parasites, immunotherapy in conjunction with chemotherapy can rapidly induce the effector immune response. With a safe and potent drug plus an affordable therapeutic vaccine (immunostimulant), which remains to be developed, a single visit by patients with visceral or cutaneous leishmaniasis might be sufficient to induce a quick and lasting recovery. Drug toxicity and the emergence of resistance could also be dramatically reduced compared with present long-term monotherapy.

Immunochemotherapy of persistent post-kala-azar dermal leishmaniasis: a novel approach to treatment.

Post-kala-azar dermal leishmaniasis (PKDL) is a recognized dermatosis that follows successful treatment of visceral leishmaniasis in the Sudan. This randomized and double-blind study aimed to assess safety, immunogenicity and curative potentials of a novel immunochemotherapy regimen in patients with persistent PKDL. Following informed consent, 30 patients were randomized to receive alum-precipitated autoclaved Leishmania major (Alum/ALM) vaccine+Bacille Calmette-Guérin (BCG) and sodium stibogluconate (SSG) or vaccine diluent and SSG.

Safety and immunogenicity of a candidate vaccine for visceral leishmaniasis (Alum-precipitated autoclaved Leishmania major + BCG) in children: an extended phase II study.

Background: Untreated visceral leishmaniasis (VL) is an inevitably fatal childhood disease. First-generation candidate vaccines for VL [autoclaved Leishmania major (ALM) + BCG] have been found to be safe and immunogenic but not superior to BCG alone. Modulation of ALM by adsorption to Alum significantly increases the immunogenicity.

Visceral leishmaniasis: new health tools are needed.

Half a million new cases of visceral leishmaniasis occur each year, and 10% of these are fatal. New tools are urgently needed for mapping, diagnosing, and treating the disease.