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BackgroundBurkitt’s lymphoma (BL) is an aggressive form of B-cell non-Hodgkin lymphoma. Endemic subtype of the disease showed a remarkable statistical and epidemiological association with malaria infection. Despite the numerous studies performed to explain this association; molecular mechanisms underlie such coincidence still remain unclear. Dissecting molecular mechanisms which link Malaria infection and Burkitt’s lymphoma can provide insights about reported anticancer action of certain antimalarial drugs, namely artemisinin derivatives.MethodsHere we applied an integrative approach to investigate for potential links between malaria infection and endemic Burkitt’s lymphoma regarding their gene expression, and further explore common molecular mechanisms through which artemisinin compounds might act in endemic Burkitt’s lymphoma. Using gene expression data of malaria (Plasmodium falciparum infected erythroblasts) and endemic Burkitt’s lymphoma from Gene Expression Omnibus database, expression patterns in the two conditions were examined through clustering analysis using Self Organizing Maps, and then by significance testing of differentially expressed genes in each condition followed by Functional annotation using Gene Ontology clustering and Pathways analysis.ResultsClustering analysis identified a significant overlap between the expression patterns in endemic Burkitt’s lymphoma and Plasmodium falciparum infected cells. Four out of the 12 identified clusters contained genes with similar expression patterns in both conditions. Differential expression analysis identified 1689 genes as significantly differentially expressed in endemic Burkitt’s lymphoma and 405 in malaria. Those genes were found to be related to important Gene Ontology terms and pathways. Interestingly 65% of the identified pathways in Malaria were overlapped with those identified in endemic Burkitt’s lymphoma. Several of these pathways reported to be related to actions of artemisinin derivatives.ConclusionOur In-silico analysis showed a significant molecular convergence between endemic Burkitt’s lymphoma and malaria. A number of 43pathways which demonstrated enrichment in tumour were shared with Plasmodium falciparum infected erythrocytes. Such pathways represent potential targets for antimalarial drugs to exert therapeutic effects in such malignancy.

International audience; Background: Infantile neuroaxonal dystrophy (INAD) is a rare hereditary neurological disorder caused by mutations in PLA2G6. The disease commonly affects children below 3 years of age and presents with delay in motor skills, optic atrophy and progressive spastic tetraparesis. Studies of INAD in Africa are extremely rare, and genetic studies from Sub Saharan Africa are almost non-existent.Case presentation: Two Sudanese siblings presented, at ages 18 and 24 months, with regression in both motor milestones and speech development and hyper-reflexia. Brain MRI showed bilateral and symmetrical T2/FLAIR hyperintense signal changes in periventricular areas and basal ganglia and mild cerebellar atrophy. Whole exome sequencing with confirmatory Sanger sequencing were performed for the two patients and healthy family members. A novel variant (NM_003560.2 c.1427 + 2 T > C) acting on a splice donor site and predicted to lead to skipping of exon 10 was found in PLA2G6. It was found in a homozygous state in the two patients and homozygous reference or heterozygous in five healthy family members.Conclusion: This variant has one very strong (loss of function mutation) and three supporting evidences for its pathogenicity (segregation with the disease, multiple computational evidence and specific patients’ phenotype). Therefore this variant can be currently annotated as “pathogenic”. This is the first study to report mutations in PLA2G6 gene in patients from Sudan.

International audience; Background: Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL, OMIM #611105) is a genetic disease of the central nervous system characterized by lower limb spasticity, cerebellar ataxia and involvement of the dorsal column. The disease is caused by mutations in the DARS2 gene but has never been reported in sub-Saharan Africa so far.Case presentation: Two siblings, aged 18 years and 15 years, from a consanguineous family presented with pyramidal signs and symptoms since infancy and developmental delay. Whole exome sequencing of the proband identified two compound heterozygous variants (NM_018122.4:c.1762C > G and c.563G > A) in DARS2. Sanger sequencing confirmed the presence of the mutations and their segregation in trans in both patients and in their elder sister (aged 20 years), who showed only brisk reflexes and mild lower limb spasticity. Surprisingly, in contrast to her subtle clinical presentation, the elder sister had abnormal MRI features and serum lactate levels comparable to her ill sisters.Conclusion: This report illustrates intra-familial phenotypic variation in LBSL and provides an example of a marked dissociation between the clinical and radiological phenotypes of the disease. This may have implications for the detection of mutation carriers in LBSL.

A group of SNPs in 5q31, genotyped from Hausa tribe of Koka village in eastern Sudan; an area endemic with malaria and visceral leishmaniasis, were analyzed by The Leishmaniasis research group and found to have significant excess of heterozygosis level and departure from HWE and assumed to be due to natural selection resulting from notorious deadly outbreaks since various ethnic groups from western Sudan settled the area although sequence information in the 5q31 region did not detect functional SNPs that could be associated with such drastic phenotypes. Malaria was thought to inflict inferior selective pressure due to the mild clinical phenotype observed. Taking advantage of follow up phenotype data sets available from the Malaria Gen study we re-analyzed these genotypes using different bioinformatics software to determine their effect on the regulation, function and expression of interleukins, miRNA binding and splicing mechanism. The SNPs were found to potentially affect the binding of many transcription factors that regulate the expression of IL-4 and IL-13 and stability of IL-5 mRNA. Association of haplotypes susceptibility revealed that the haplotype of low cytokine TH2 profile is associated with higher risk of malaria infection (P-value = 0.02). Through modulating TH2 cytokine response; the excess heterozygosity in 5q31 is explained with the phenomenon of overdominance between malaria and visceral leishmaniasis, acted by natural selection and driving the locus towards optimum response.

BACKGROUND Due to the recently observed rise in Plasmodium vivax incidence in Sudan and reported transmission in Duffy-negative individuals; we aimed to assess the possibility of P. vivax transmission in Duffy-negative individuals in Gezira state, central Sudan. METHOD A total of 126 suspected malaria patients were diagnosed with P. vivax infection using microscopy, RDT and PCR. PCR-RFLP was used to genotype participants Duffy status. RESULTS Forty eight (38%) were positive for P. vivax infection by PCR. Four patients (8.3%) were homozygous Duffy-negative. CONCLUSION These results confirm that P. vivax can infect Duffy-negative individuals, suggesting alternative mechanisms to bind and invade erythrocytes.

Recent understanding of the genetic basis of neurological disorders in Africa has grown rapidly in the last two decades. Africa harbors the largest genetic repertoire in the world which gives unique opportunity to discover novel variant, genes, and molecular pathways associated with various neurological diseases. Despite that, large-scale genomic and exome studies are severely lacking especially for neglected diseases such as leukodystrophies. This review aims to shed light on the currently developed research in leukodystrophies in Africa. We reviewed all research articles related to “Leukodystrophy in Africa” published in Medline/PubMed and Google Scholar databases up to date. We found very few studies in leukodystrophy from Africa, especially from the Sub-Saharan regions. Metachromatic leukodystrophy was the most studied type of leukodystrophy. Published studies from North Africa (Tunisia, Morocco, and Egypt) were very limited in either sample size (case studies or single/few family studies) or molecular methods (targeted sequencing or polymerase chain reaction-restriction fragment length polymorphisms). More studies (GWAS or large family studies) with advanced techniques such as exome or whole genome sequencing are needed to unveil the genetic basis of leukodystrophy in Africa. Unmasking novel genes and molecular pathways of leukodystrophies invariably lead to better detection and treatment for both Africans and worldwide populations.

Plasmodium falciparumis a predominant malaria species that infects humans in the African continent. A recent WHO report estimated 95% and 5% ofP. falciparumandP. vivaxmalaria cases, respectively, in Sudan. However many laboratory reports from different areas in Sudan indicated otherwise. In order to verify, we selected four hundred suspected malaria cases from Aljabalain area located in the White Nile state, central Sudan, and diagnosed them with quality insured microscopy and species-specific nested PCR. Our results indicated that the proportion ofP. vivaxinfections among suspected malaria cases was high. We found that on average 20% and 36.5% of malaria infections in both study areas were caused byP. vivaxusing both microscopy and PCR, respectively. This change in pattern is likely due to the recent demographic changes and high rate of immigration from neighbouring countries in the recent years. This is the first extensive clinical study of its kind that shows rising trend inP. vivaxmalaria cases in White Nile area, Sudan.

Background: Malaria is a major health problem, with over one third of worldwide populations currently at risk. Determining the genetic diversity of plasmodium parasites is essential for assessing the efficacy of antimalarial drugs and for future vaccine development. This study investigated the genetic diversity of P. falciparum merozoite surface protein 2 (MSP2), and multiplicity of infection (MOI) in different geographic regions in Sudan. Methods: A total of 271 patients with uncomplicated malaria were recruited from four ecological sites during malaria transmission season, 2011-2013. P. falciparum was confirmed using species specific primers targeting the rDNA gene. All P. falciparum positive samples were genotyped for the major MSP2 allelic families (IC1/3D7 and FC27 MSP2 allele) using nested PCR. Multiplicity of infection and allele frequencies were determined. Results: A total of 241 samples (88.9%) were confirmed positive for P. falciparum. The number of different MSP2 alleles were 14, 15, 13 and 12 in Khartoum, Gezira, River Nile and Red Sea states, respectively. The 3D7 allelic family was more prevalent in the states of Khartoum, Gezira, River Nile and Red Sea compared to the FC27 allelic family. Multiclonal infections were observed in 25.8% of patients, with a mean multiplicity of infection (MOI) of 1.45. MOIs were highest in the age group over 40, with an average of 2 and 1.68 in Khartoum and Gezira states, respectively, however MOIs in River Nile and Red Sea states were higher in age groups below 18, with an average of 1.37 and 1.33, respectively. Conclusions: MSP2 allelic genotyping revealed MOI and diversity of the Sudanese P. falciparum isolates. The results of our study are expected to influence current and future malaria control strategies, since the MOI predicts development of clinical malaria and subsequent efficacy of antimalarial treatment.

Background Multiplicity and genetic diversity of Plasmodium falciparum infection might play a role in determining the clinical outcome of malaria infection and could be a fair reflection of the disease transmission rate. This study investigated the genetic diversity of P. falciparum and multiplicity of infection in relation to the severity of malaria and age of patients in Gezira State, Sudan. Methods A cross-sectional health facilities-based survey was conducted in Gezira State, Sudan in January 2012. A total of 140 P. falciparum malaria patients diagnosed with microscopy and confirmed using nested PCR were recruited and classified into uncomplicated malaria and severe malaria states according to the standard WHO criteria. DNA was extracted and MSP1 and MSP2 allelic families were determined using nested PCR. Results The overall multiplicity of infection (MOI) was 2.25 and 2.30 and 2.15 for uncomplicated and severe malaria respectively. There were no statistically significant differences between uncomplicated and severe malaria (SM) patient groups in MOI with regard to MSP1, MSP2 and overall MOI (Mann-Whitney U-test; all P