Safety and Effectiveness of Sodium Stibogluconate and Paromomycin Combination for the Treatment of Visceral Leishmaniasis in Eastern Africa: Results from a Pharmacovigilance Programme.

Introduction: In 2010, WHO recommended a new first-line treatment for visceral leishmaniasis (VL) in Eastern Africa. The new treatment, a combination of intravenous (IV) or intramuscular (IM) sodium stibogluconate (SSG) and IM paromomycin (PM) was an improvement over SSG monotherapy, the previous first-line VL treatment in the region. To monitor the new treatment's safety and effectiveness in routine clinical practice a pharmacovigilance (PV) programme was developed.

The Leishmaniasis East Africa Platform (LEAP): strengthening clinical trial capacity in resource-limited countries to deliver new treatments for visceral leishmaniasis.

Visceral leishmaniasis is a neglected tropical disease endemic in East Africa where improved patient-adapted treatments are needed. The Leishmaniasis East Africa Platform (LEAP) was created in 2003 to strengthen clinical research capacity, serve as a base for training, and evaluate and facilitate implementation of new treatments. Major infrastructure upgrades and personnel training have been carried out.

Safety and efficacy of single dose versus multiple doses of AmBisome for treatment of visceral leishmaniasis in eastern Africa: a randomised trial.

Background: Anti-leishmanial drug regimens that include a single dose AmBisome could be suitable for eastern African patients with symptomatic visceral leishmaniasis (VL) but the appropriate single dose is unknown.

Methodology: A multi-centre, open-label, non-inferiority, randomized controlled trial with an adaptive design, was conducted to compare the efficacy and safety of a single dose and multiple doses of AmBisome for the treatment of VL in eastern Africa. The primary efficacy endpoint was definitive cure (DC) at 6 months.

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.

Survey of causative agents for acute respiratory infections among patients in Khartoum-State, Sudan, 2010-2011.

Background: This study was carried out to determine causative agents of acute respiratory illness of patients in Khartoum State, Sudan.

Methods: Four hundred patients experiencing respiratory infections within January-March 2010 and January-March 2011 were admitted at Khartoum Hospital and had their throat swab samples subjected to multiplex real-time RT-PCR to detect influenza viruses (including subtypes) and other viral agents. Isolation, nucleotide sequence and phylogenetic analysis on some influenza viruses based on the HA gene were done.

Azadirachta indica ethanolic extract protects neurons from apoptosis and mitigates brain swelling in experimental cerebral malaria.

Background: Cerebral malaria is a rapidly developing encephalopathy caused by the apicomplexan parasite Plasmodium falciparum. Drugs currently in use are associated with poor outcome in an increasing number of cases and new drugs are urgently needed. The potential of the medicinal plant Azadirachta indica (Neem) for the treatment of experimental cerebral malaria was evaluated in mice.

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.

Aflatoxin M₁ in breast milk of nursing Sudanese mothers.

The presence of aflatoxin M1 (AFM1) in the breast milk of nursing Sudanese mothers was investigated using AOAC official method 980.21 as the extraction method and HPLC with fluorescence detector for separation and detection. Following informed consent, 94 breast milk samples of mothers were collected, and 51 samples were found to be positive for AFM1, with an average concentration of 0.

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.

Immunogenicity and immune modulatory effects of in silico predicted L. donovani candidate peptide vaccines.

Visceral leishmaniasis (VL) is a serious parasitic disease for which control measures are limited and drug resistance is increasing. First and second generation vaccine candidates have not been successful. The goal of the present study was to select possibly immunogenic L.

Genetic and functional evidence implicating DLL1 as the gene that influences susceptibility to visceral leishmaniasis at chromosome 6q27.

Background: Visceral leishmaniasis (VL) is caused by Leishmania donovani and Leishmania infantum chagasi. Genome-wide linkage studies from Sudan and Brazil identified a putative susceptibility locus on chromosome 6q27.

Methods: Twenty-two single-nucleotide polymorphisms (SNPs) at genes PHF10, C6orf70, DLL1, FAM120B, PSMB1, and TBP were genotyped in 193 VL cases from 85 Sudanese families, and 8 SNPs at genes PHF10, C6orf70, DLL1, PSMB1, and TBP were genotyped in 194 VL cases from 80 Brazilian families.

Safety and efficacy of miltefosine alone and in combination with sodium stibogluconate and liposomal amphotericin B for the treatment of primary visceral leishmaniasis in East Africa: study protocol for a randomized controlled trial.

Background: Treatment options for visceral leishmaniasis (VL) in East Africa are far from satisfactory due to cost, toxicity, prolonged treatment duration or emergence of parasite resistance. Hence there is a need to explore alternative treatment protocols such as miltefosine alone or in combinations including miltefosine, sodium stibogluconate (SSG) or liposomal amphotericin B. The aim of this trial is to identify regimen(s) which are sufficiently promising for future trials in East Africa.

Single-dose liposomal amphotericin B (AmBisome®) for the treatment of visceral leishmaniasis in East Africa: study protocol for a randomized controlled trial.

Background: AmBisome® is an efficacious, safe anti-leishmanial treatment. There is growing interest in its use, either as a single dose or in combination treatments. In East Africa, the minimum optimal single-dosage has not been identified.

Anti-plasmodial effects of Azadirachta indica in experimental cerebral malaria: Apoptosis of cerebellar Purkinje cells of mice as a marker.

Background: Malaria is a major public health problem in the world, but treatment of malaria is becoming more difficult due to increasing drug resistance. Therefore, the need for alternative drugs is acute.

Aims: This study investigated the antiplasmodial and protective effect of an ethanolic extract of the leaves from a traditionally used medicinal plant, Azadirachta indica (Neem) in a mouse model of malaria.

Loss of balancing selection in the betaS globin locus.

Background: Probably the best example of the rise and maintenance of balancing selection as an evolutionary trend is the role of S-haemoglobin (HbS - rs334) in protecting from malaria. Yet, the dynamics of such a process remains poorly understood, particularly in relation to different malaria transmission rates and the genetic background of the affected populations.

Methods: We investigated the association of haemoglobin HbS in protection from clinical episodes of malaria in two populations/villages where malaria is endemic, but mostly presenting in mild clinical forms.

Evaluation of the particle gel diffusion technique for the detection of haemoglobin S in Sudanese patients.

Background: Sickle cell disease is a heterogenous disorder characterized by an abnormal haemoglobin and sickling phenomena of red cells. It is prevalent among certain nomadic tribes in Sudan. Painful, aplastic and haemolytic crises mark sickle cell anaemia.

First generation leishmaniasis vaccines: a review of field efficacy trials.

First generation candidate vaccines against leishmaniasis, prepared using inactivated whole parasites as their main ingredient, were considered as promising because of their relative ease of production and low cost. These vaccines have been the subject of many investigations over several decades and are the only leishmaniasis vaccine candidates which have undergone phase 3 clinical trial evaluation. Although the studies demonstrated the safety of the vaccines and several studies showed reasonable immunogenicity and some indication of protection, an efficacious prophylactic vaccine is yet to be identified.

Innovative serum-free medium for in vitro cultivation of promastigote forms of Leishmania species.

We described a comparatively simple medium formula (CML) using common, available and reasonably priced ingredients that could be used in place of medium that requires calf serum enhancement for cultivation of Leishmania promastigote forms. This medium equivalently supported the growth of parasites at rates comparable with those obtained with serum supplemented RPMI-1640 medium. Leishmania promastigotes reproduced in CML exhibited moderate to high infectivity capacities when tested against J774 macrophage cell line.

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.

Pattern of glomerulonephritis in Sudan: histopathological and immunofluorescence study.

The final diagnosis of renal disease can only be established with the study of renal biopsy using light microscopy, immunohistochemistry and electron microscopy. This study reports on the pattern of glomerulonephritis, diagnosed with light microscopy and immunofluorescence, in two major nephrology referral centers in Sudan. Renal biopsies from 86 consecutive patients were studied by light and immunofluorescence microscopy.

Y chromosome lineage- and village-specific genes on chromosomes 1p22 and 6q27 control visceral leishmaniasis in Sudan.

Familial clustering and ethnic differences suggest that visceral leishmaniasis caused by Leishmania donovani is under genetic control. A recent genome scan provided evidence for a major susceptibility gene on Chromosome 22q12 in the Aringa ethnic group in Sudan. We now report a genome-wide scan using 69 families with 173 affected relatives from two villages occupied by the related Masalit ethnic group.

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.

Antimony-induced cerebellar ataxia.

Visceral leishmaniasis VL, caused by Leishmania donovani is endemic over several parts of Sudan. The disease is fatal if not treated. Although sodium stibogluconate Pentostam, a pentavalent antimonial is not free from toxicity, it has been in use for treatment of VL for the last 50 years.