Distribution of fusion transcripts and its clinical impact in patients with acute myeloid leukemia in Sudan.

OBJECTIVE: Acute myeloid leukemia (AML) is a common malignant disorder of hematopoietic progenitor cells that caused by chromosomal translocation and the formation of fusion oncogenes. This study determined the frequencies of fusion genes in Sudanese patients with AML and their clinical impacts. METHODS: This study was conducted at Alzaeim Alazhari University, Khartoum, Sudan. A total of 97 patients with AML were recruited in the study from different clinics in Khartoum state. Quantitative real-time polymerase chain reaction was used to determine types of fusion genes. RESULTS: The highest frequency of genetic defects was observed for AML1-ETO fusion gene (57.6%) followed by MLL-AF9 (35.1%) and FUS-ERG (7.2%). No significant differences in blast cells, hemoglobin, total white blood cells, and platelets were found between different gene fusion groups (P > 0.05). In addition, no differences in the frequency of splenomegaly, hepatomegaly and lymphadenopathy were observed between different gene fusion groups (P > 0.05). With respect to French-American-British (FAB) classification, the M2 and M3 were significantly higher in patients with AML1-ETO fusion (86%, P < 0.01) whereas M4 and M5 were higher in patients with MLL-AF9 fusion (76.5%, P < 0.01). CONCLUSIONS: The study concluded that AML1-ETO and MLL-AF9 fusion genes were predominant in AML Sudanese patients. None of the examined clinical parameters were different between different fusion genes except for FAB stages.

Evaluation of a rapid diagnostic test for Schistosoma mansoni infection based on the detection of circulating cathodic antigen in urine in Central Sudan.

BACKGROUND: The Kato-Katz thick smear is the standard test for the diagnosis of Schistosoma mansoni infection, but the sensitivity of this technique is low. As an alternative, (CCA) strip test has been evaluated with the conclusion that it may replace the Kato-Katz method in areas where prevalences are moderate or high. Therefore, this study was undertaken to evaluate the performance of the CCA strip test in the diagnosis and monitoring of S. mansoni infection in Sudan. METHODOLOGY: 489 stool and urine samples were collected from school children in endemic area of Sudan to determine the validity of CCA strip test based on duplicate Kato-Katz thick smear technique. Additional, 118 samples from known non schistosome-endemic area were collected to assess the CCA cross reactivity with other pathogens rather than schistosomiasis. The stability of CCA in urine samples was determined by consecutive examination of 40 positive CCA urine samples. 81 samples were used to evaluate the CCA strip test for the assessment of cure one week, three weeks and six weeks post Praziquantel treatment. PRINCIPAL FINDINGS: Assuming parasitological test results as the gold standard, the sensitivity, specificity, positive predictive and negative predictive values of the CCA test were 96%, 85.4%, 78.5% and 97.5% respectively. There was no cross reactivity with other pathogens. The CCA strip test showed high accuracy in monitoring of treatment 93.8% and 100% after three and six weeks of administration of Praziquantel respectively. The stability of the CCA for long time in the urine revealed a safety transportation and shipment of the samples whenever it demanded. CONCLUSION/SIGNIFICANCE: The uses of urine CCA strip test in the field would provide more accurate information on the epidemiology and monitoring of the Schistosoma mansoni infection in endemic areas of schistosomiasis than the conventional parasitological method. Moreover, The stability of CCA in urine samples confirms a safety transportation period of the samples whenever it required.

Plasmodium vivax cerebral malaria in an adult patient in Sudan.

BACKGROUND: Plasmodium vivax infection is rising in sub-Saharan Africa, where Plasmodium falciparum is responsible for more than 90% of malaria cases. While P. vivax is identified as a major cause of severe and cerebral malaria in South east Asia, the Pacific and South America, most of the severe and cerebral cases in Africa were attributed to P. falciparum. Cases of severe malaria due to P. vivax are emerging in Africa. A few severe P. vivax cases were reported in Eastern Sudan and they were underestimated due to the lack of accurate diagnosis, low parasitaemia and seldom use of rapid diagnostic tests (RDTs). CASE PRESENTATION: A 60-year-old Sudanese male presented to the Al Kuwaiti hospital in the Sudan capital Khartoum. On admission, the patient was complaining of fever (measured temperature was 38 °C), sweating, chills, vomiting and confusion in the past 2 days prior to his admission. He rapidly deteriorated into a coma state within 48 h of the admission, with significant neck stiffness. He was admitted to the intensive care unit and was suspected of meningitis. Lumbar puncture was not performed since the patient was suffering from spinal cord disc. Brain CT scan was unremarkable. Several biochemical, haematological tests, and blood film for malaria were performed. The results of the laboratory tests were within the normal range except of mild elevation of the total white blood cell count and a significant decrease in the platelets count. Malaria parasites were seen in the blood film with high parasitaemia (quantified as 3 +++). The patient was diagnosed as P. vivax cerebral malaria based on the positive blood film and the amplification of P. vivax specific 499 bp amplicon using Plasmodium multi-species multiplex Polymerase Chain Reaction (PCR). The patient was treated with quinine 10 mg/kg body weight for 10 days followed by primaquine 15 mg/days PO for 2 weeks. The symptoms subsided within 48 h and the patients was cured and released from the hospital. CONCLUSIONS: Plasmodium vivax is an emerging cause of cerebral malaria in adults in Sudan and should be considered in the differential diagnosis of cerebral malaria for proper management of patients.

Association of Epstein - Barr virus and breast cancer in Eritrea.

BACKGROUND: The oncogenic potential of Epstein-Barr virus (EBV) in breast cancer is being increasingly recognized. Despite some controversies regarding such role, new evidence is suggesting a culpability of EBV in breast cancer, particularly in Africa where the virus has been originally associated with causation of several solid and hematological malignancies. One example is a report from Sudan implicating EBV as a prime etiologic agent for an aggressive type of breast cancer, where nearly 100% of tumor tissues were shown to carry viral signatures. To get a broader view on such association, other nearby countries should be investigated. The present study aims to determine the prevalence and possible associations of the virus in Eritrean breast cancer patients. METHODS: Detection of EBV genome using primers that target Epstein Barr Encoded RNA (EBER) gene and Latent Membrane Protein-1 (LMP-1) gene sequences was performed by polymerase chain reaction (PCR) on DNA samples extracted from 144 formalin fixed paraffin embedded breast cancer tissues and 63 non-cancerous breast tissue as control group. A subset of PCR positive samples was evaluated for EBER gene expression by in situ hybridization (ISH). Expression of Latent Membrane Protein-2a (LMP2a) was also assessed by immunohistochemistry in a subset of 45 samples. RESULTS: Based on PCR results, EBV genome signals were detected in a total of 40 samples (27.77%) as compared to controls (p-value = 0. 0031) with a higher sensitivity when using the EBER primers. Five out of the 14 samples stained by EBER-ISH 35.71% were positive for the virus indicating the presence of the viral genome within the tumor cells. Of those stained for IHC 7 (15.55%) were positive for LMP2a showing low viral protein frequency. CONCLUSIONS: Based on these findings it can be concluded that EBV in Eritrea is associated with a smaller subset of tumors, unlike neighboring Sudan, thus pointing to possible differences in population predisposition and diseases epidemiology.

Myasthenic Crisis Manifesting as Postoperative Respiratory Failure following Resection of Unsuspected Intrathoracic Thymic T-Cell Lymphoma during Thyroidectomy for an Adjacent Large Retrosternal Goiter.

A middle-aged female with a goiter of 10 years' duration presented with progressive pressure symptoms, nocturnal choking and dyspnea on exertion for 5 months. Physical examination demonstrated a large simple multinodular goiter. Imaging revealed a deep retrosternal goiter extending below the tracheal bifurcation with marked tracheal deviation. Total thyroidectomy was carried out via a cervical approach and a median sternotomy. Extubation was not possible, and the patient had to be kept intubated. She then went into a myasthenic crisis. Initial ventilatory support was followed by intravenous immunoglobulin, steroids and pyridostigmine. The patient had complete remission and was asymptomatic 18 months later. Histopathology showed a T-cell-rich thymoma in addition to a nodular colloid goiter.

Re-examination of renal allograft biopsy blocks for C4d positivity: missed cases of antibody mediated rejection.

INTRODUCTION: C4d immunostaining of renal allograft biopsies is recommended for the diagnosis of antibody-mediated rejection (ABMR), but it was not available to us prior to June 2012. In June 2012, we were able to obtain anti-human C4d polyclonal antibody and decided to retrospectively evaluate archived kidney allograft biopsies at our center for C4d deposition. METHODS: Twenty-four paraffin blocks were available for this study. Immunostaining for C4d was performed using anti-human C4d polyclonal antibody by Immunohistochemistry. The score and pattern of C4d positivity were determined according to the Banff 2007 guidelines. RESULTS: All grafts were from living related donors with negative CDC cross-match. The indications for biopsy were primary, acute and chronic graft dysfunction in 29.2%, 33.3% and 37.5% of patients respectively. Two biopsies revealed extensive necrosis rendering it difficult to interpret the result of C4d staining. Among the remaining 22 biopsies, C4d staining was categorized as negative in 40.9%, minimal in 13.6%, focal in 22.7% and diffuse in 22.7%. The prevalence of C4d positivity among biopsies taken due to primary, chronic and acute graft dysfunction was 71.4%, 44.4% and 12.5% respectively. CONCLUSION: C4d positivity was common in biopsies taken from this group of kidney transplant recipients and its prevalence was particularly high among biopsies taken due to primary graft non-function. This indicates that missed ABMR is an important cause for kidney allograft dysfunction in our setting.

Mucosal leishmaniasis in a Sudanese patient.

Mucosal leishmaniasis (ML) is an oral disease caused by the parasite Leishmania donovani. The disease has been proven to be pandemic in many areas of the world. It affects young men living in leishmaniasis-endemic areas. ML might be accompanied or proceeded by visceral leishmaniasis (VL), although in most of the cases seen in Sudan, ML occurs as a primary lesion. ML can mimic oral cancer or fungal infections, with ulceration as the most common finding in ML lesions. In this report, the patient came from an area known to be endemic for VL. Although the lesions were not ulcerative, the patient history was indicative for ML. Early detection and proper diagnosis were of great help in the cure and prognosis of the disease.

Addison's disease due to Histoplasma duboisii infection of the adrenal glands.

Histoplasmosis is a fungal infection caused by Histoplasma capsulatum. In the normal individual, both disseminated histoplasmosis and symptomatic adrenal histoplasmosis are rare. Herein, we describe the case of a 50-year-old gentleman residing in western Sudan who presented with a 7-month history of generalized body weakness, easy fatigue, and frequent attacks of vomiting and diarrhea. Physical examination and laboratory investigations confirmed the diagnosis of Addison's disease due to Histoplasma capsulatum var duboisii infection of the adrenal glands. He was treated with intravenous hydrocortisone, followed by oral prednisolone and itraconazole.

Sudanese mucosal leishmaniasis: isolation of a parasite within the Leishmania donovani complex that differs genotypically from L. donovani causing classical visceral leishmaniasis.

Mucosal leishmaniasis, which is a sporadic disease in the Sudan, was shown by isoenzyme characterization and PCR to be caused by Leishmania donovani. However, it was not clear if the parasite was exactly the same strain as that causing visceral leishmaniasis (VL), or of a different strain. We utilized a new generation of molecular DNA markers, minisatellites and kinetoplast DNA, for rapid characterization of the parasite. The results show that the genotypes of some of the parasites causing VL are different from those causing mucosal leishmaniasis. The L. donovani isolates causing visceral disease, as well as post-kala-azar mucosal leishmaniasis (PKML), have been shown to possess characteristic haplotypes. However, sequencing of a portion of the cytochrome oxidase II (COII) gene indicates that the parasite that invades the oral mucosa is divergent from other parasites causing VL. It appears to possess features of a more ancestral parasite with pronounced sequence homology to L. major. This agrees with earlier studies where isolates of mucosal leishmaniasis have been shown to possess an isoenzyme profile distinct from L. donovani and a different geographical distribution, albeit often overlapping with that of L. donovani.