Evaluating utility and feasibility of mismatch repair testing of colorectal cancer patients in a low-middle-income country.

Molecular pathology services for colorectal cancer (CRC) in Sudan represent a significant unmet clinical need. In a retrospective cohort study involving 50 patients diagnosed with CRC at three major medical settings in Sudan, we aimed to outline the introduction of a molecular genetic service for CRC in Sudan, and to explore the CRC molecular features and their relationship to patient survival and clinicopathological characteristics. Mismatch repair (MMR) and BRAF (V600E) mutation status were determined by immunohistochemistry. A mismatch repair deficient (dMMR) subtype was demonstrated in 16% of cases, and a presumptive Lynch Syndrome (LS) diagnosis was made in up to 14% of patients. dMMR CRC in Sudan is characterized by younger age at diagnosis and a higher incidence of right-sided tumours. We report a high mortality in Sudanese CRC patients, which correlates with advanced disease stage, and MMR status. Routine MMR immunohistochemistry (with sequential BRAF mutation analysis) is a feasible CRC prognostic and predictive molecular biomarker, as well as a screening tool for LS in low-middle-income countries (LMICs).

MERS-CoV in Camels but Not Camel Handlers, Sudan, 2015 and 2017.

We tested samples collected from camels, camel workers, and other animals in Sudan and Qatar in 2015 and 2017 for evidence of Middle East respiratory syndrome coronavirus (MERS-CoV) infection. MERS-CoV antibodies were abundant in Sudan camels, but we found no evidence of MERS-CoV infection in camel workers, other livestock, or bats.

Immunohistochemistry defined subtypes of breast cancer in 678 Sudanese and Eritrean women; hospitals based case series.

BACKGROUND: Breast cancer is the most common malignancy accounting for 25% of all cancers in females. In Africa, breast cancer prevalence and mortality are steadily increasing. Knowledge of hormone receptors and human epidermal growth factor receptor-2 (HER-2) expressions are vital for breast cancer management plans and decision making. There is wide regional variation in the proportion of these biomarkers, especially in African countries. Hormone receptors positivity in indigenous African and African American women is considered to be low and triple negative breast cancer is a dominant phenotype. There is paucity of data regarding hormone receptors (ER and PR) and HER2 expressions in North-eastern Africa (Eritrea and Sudan). The purpose of this study was to evaluate the expression of ER, PR and HER2 in Eritrean and Sudanese case series and correlate these biomarkers with the clinicopathological profile. METHOD: Clinicopathologic data of patients were collected from clinical records. Immunohistochemistry biomarkers (ER, PR, and HER2) were assessed in consecutive female patients who had been diagnosed with invasive breast cancer from 2011 to 2015 in Gezira University Pathology Laboratory, the Sudan and National Health laboratory, Asmara, Eritrea. RESULTS: There were 678 cases involved in this study. The mean age was 48.8 years with ±0.53 standard error of the mean. Two-thirds of the case were ≤50 years. Invasive ductal carcinoma, no special type was the most dominant histologic type (86%) in both study groups. The majority of cases (70%) had tumour stage pT2 and pT3 and about 50% had lymph node involvement. Less than 5% of the cases had well-differentiated tumours. The ER, PR and HER2 positive rates were 45%, 32%, and 29%, respectively. The proportion of luminal-A like, luminal-B like, HER2 enriched and TNBC were 37%, 13%, 16% and 34%, respectively. Fisher extract analysis showed age (p = .015), tumour size (p = .041), and histologic grade (p = .000) were significantly associated with intrinsic subtypes. Furthermore, Logistic regression analysis stratified by origin, age, tumour size, lymph-node metastasis and grade indicated that younger women age (≤50 years) and grade III tumours were more likely to be diagnosed with ER negative breast cancer. CONCLUSION: Most of Sudanese and Eritrean women were diagnosed at younger age and with unfavourable prognostic clinicopathologic prognostic markers. TNBC is more frequent in this cohort study; patients with grade III tumours and young age are more likely to be hormone receptors negative. Therefore, routine determination of hormone receptors is warranted for appropriate targeted therapy.

Recommendations for dealing with waste contaminated with Ebola virus: a Hazard Analysis of Critical Control Points approach.

OBJECTIVE: To assess, within communities experiencing Ebola virus outbreaks, the risks associated with the disposal of human waste and to generate recommendations for mitigating such risks. METHODS: A team with expertise in the Hazard Analysis of Critical Control Points framework identified waste products from the care of individuals with Ebola virus disease and constructed, tested and confirmed flow diagrams showing the creation of such products. After listing potential hazards associated with each step in each flow diagram, the team conducted a hazard analysis, determined critical control points and made recommendations to mitigate the transmission risks at each control point. FINDINGS: The collection, transportation, cleaning and shared use of blood-soiled fomites and the shared use of latrines contaminated with blood or bloodied faeces appeared to be associated with particularly high levels of risk of Ebola virus transmission. More moderate levels of risk were associated with the collection and transportation of material contaminated with bodily fluids other than blood, shared use of latrines soiled with such fluids, the cleaning and shared use of fomites soiled with such fluids, and the contamination of the environment during the collection and transportation of blood-contaminated waste. CONCLUSION: The risk of the waste-related transmission of Ebola virus could be reduced by the use of full personal protective equipment, appropriate hand hygiene and an appropriate disinfectant after careful cleaning. Use of the Hazard Analysis of Critical Control Points framework could facilitate rapid responses to outbreaks of emerging infectious disease.

HLA polymorphism in Sudanese renal donors.

The main objective of this study is to provide a database for renal transplantation in Sudan and to determine the HLA antigens and haplotype frequencies (HFs) in the study subjects. HLA typing was performed using the complement-dependant lymphocytotoxicity test in 250 unrelated healthy individuals selected as donors in the Sudanese Renal Transplantation Program. Considerable polymorphism was observed at each locus; A2 (0.28), A30 (0.12), A3 (0.09), A24 (0.09), A1 (0.09), and A68 (0.06) were the most frequent antigens in the A locus, while B51 (0.092), B41 (0.081), B39 (0.078), B57 (0.060), B35 (0.068), B 50 (0.053) and B 52 (0.051) were the most common B locus antigens. DR13 (0.444) and DR15 (0.160) showed the highest antigen frequencies (AFs) in the DR locus. In the DQ locus, DQ1 showed the highest gene frequency (0.498), while DQ2 and DQ3 AFs were (0.185) and (0.238), respectively. The most common HLA-A and -B haplotypes in positive linkage disequilibrium were A24, B38; A1, B7; and A3, B52. The common HLA-A and -B HFs in positive linkage disequilibrium in the main three tribe-stocks of the study subjects (Gaalia, Nile Nubian and Johyna) were A24, B38 for Gaalia; A24, B38 and A2, B7 for Johyna; and A2, B64 and A3, B53 for Nile Nubian. These results suggest that both class I and class II polymorphisms of the study subjects depict considerable heterogeneity, which reflects recent admixture of this group with neighboring Arabs and African populations.

Clinical presentation and outcome of retinoblastoma among children treated at the National Cancer Institute (NCI) in Gezira, Sudan: a single Institution experience.

BACKGROUND: Retinoblastoma (RB) is a rare and unique cancer that affects the eyes of very young children. There are few reports on RB in Sudan. MATERIALS AND METHODS: We performed a retrospective study of data from patients diagnosed with retinoblastoma between January 1999 and December 2009 at the National Cancer Institute in Gezira (NCI-Gezira). RESULTS: Of the 519 cases of childhood cancer treated at NCI-Gezira during the study period, 25 (4.8%) were retinoblastoma. Of these 25 patients with retinoblastoma, there were 13 boys and 19 cases were unilateral. The median age at diagnosis was 36 months (range, 8-60 months). The disease was localized in 9 patients, regional in 5 patients, and metastatic in 11 patients. The most frequent symptoms were enlarged eye (n = 14) and leukocoria (n = 8). Nine patients (36%) have been lost to follow-up; 9 were alive at last follow-up (7 in remission, 2 progressed); and 7 have died (5 from disease and 2 from unrelated causes). Twenty-two eyes were enucleated in 16 patients (6 bilateral and 10 unilateral). Pathologic examination of the enucleated eyes could only be completed in 11 patients. Diagnostic imaging in the form of computerized tomography scans or ultrasonography of the brain and orbit was done for 10 patients (40%). CONCLUSIONS: Although these findings are not surprising, and similar to reports from other developing countries, we hope our work will provide a foundation for strategies to improve outcome for retinoblastoma in our center such as proper training, public awareness, team approach, and twinning.

Informed decision-making before changing to RDT: a comparison of microscopy, rapid diagnostic test and molecular techniques for the diagnosis and identification of malaria parasites in Kassala, eastern Sudan.

OBJECTIVES: Rapid diagnostic tests (RDTs) are promoted for the diagnosis of malaria in many countries. The question arises whether laboratories where the current method of diagnosis is microscopy should also switch to RDT. This problem was studied in Kassala, Sudan where the issue of switching to RDT is under discussion. METHODS: Two hundred and three blood samples were collected from febrile patients suspected of having malaria. These were subsequently analysed with microscopy, RDT (SD Bioline P.f/P.v) and PCR for the detection and identification of Plasmodium parasites. RESULTS: Malaria parasites were detected in 36 blood samples when examined microscopically, 54 (26.6%) samples were found positive for malaria parasites by RDT, and 44 samples were positive by PCR. Further analysis showed that the RDT used in our study resulted in a relatively high number of false positive samples. When microscopy was compared with PCR, an agreement of 96.1% and k = 0.88 (sensitivity 85.7% and specificity 100%) was found. However, when RDT was compared with PCR, an agreement of only 81.2 and k = 0.48 (sensitivity 69% and specificity 84%) was found. CONCLUSION: PCR has proven to be one of the most specific and sensitive diagnostic methods, particularly for malaria cases with low parasitaemia. However, this technique has limitations in its routine use under resource-limited conditions, such as our study location. At present, based on these results, microscopy remains the best option for routine diagnosis of malaria in Kassala, eastern Sudan.

Frequency distribution of antimalarial drug resistance alleles among Plasmodium falciparum isolates from Gezira State, central Sudan, and Gedarif State, eastern Sudan.

In 2004, Sudan adopted artesunate + sulfadoxine/pyrimethamine (SP) combination as the first-line drug, in response to the high level of falciparum resistance to antimalarials. In 2007, a molecular study on antimalarial resistance linked genes, pfcrt, pfmdr1, pfdhfr, pfdhps, and pfATPase6, was conducted on 198 isolates from central and eastern Sudan. We observed a high frequency of point mutations at almost all loci analyzed, mainly of pfcrt 76T (72.7%), pfdhfr 51I (75.3%), and pfdhfr 108N (72.7%) alleles. The MARK III in vitro test for chloroquine sensitivity in 45 P. falciparum isolates showed that 37.8% of the isolates were low resistant and 6.7% were fully resistant. This study represents the most recent molecular investigation on antimalarial resistance in this area after the adoption of artemisinin-based combination therapy (ACT), and underlines the importance of the analysis of SP resistance evolution to monitor the efficacy of ACT therapy in endemic areas.

Malaria parasitemia during delivery.

OBJECTIVE: The aim of this study is to investigate the impact of plasmodium falciparum infection in parturient women in Central Sudan where malaria transmission is mesoendemic. The purpose of this paper is to find out the prevalence of malaria parasitemia and the risk of anemia among parturient women and to suggest appropriate strategies to lower their prevalence rates. METHODS: This prospective study was conducted at Medani Teaching Hospital, Sudan, a tertiary regional referral center, during the period January 1997 through to December 1997. All cases were admitted during labor to the delivery room and were clinically suspected to have malaria. History, examination and investigations were carried out on all patients. RESULTS: The total number of patients enrolled in this study was 550, amounting to 14.9% of all women (N=3,687) who delivered during the study period. The prevalence of malaria parasitemia was 58.9% (N=550) while prevalence of anemia (defined as hemoglobulin <9.0 g/dl) was 24.1%. The mean hemoglobulin levels in patients with positive and negative malaria parasitemia was 9.72 1.62 and 9.85 1.60 g/dl. Statistically the difference in the mean hemoglobulin level was not significant, t=0.879, (P>0.05). A significant negative correlation between parasite count in maternal blood and hemoglobulin level of the mother, was observed, where r=-0.121 (P=0.032). Out of 17 (3.3%) patients who had used chloroquine tablets for prophylaxis, 11 patients still had positive parasitemia. Although there was a higher parasite count in those 11 patients, statistically the difference was not significance where P> 0.05. CONCLUSION: The study documents a high prevalence of malaria parasitemia and anemia among the parturient women in Central Sudan. There were 533 pregnant women (97%) who did not use chloroquine tablets as chemoprophylaxis and 17 (3%) had prophylaxis. Eleven of the later (N=17) had positive parasitemia. In view of the high prevalence of parasitemia and anemia, and although the sample of patients who used chloroquine tablets for prophylaxis and had positive parasitemia is small (17 out of 550), a wide scale prophylaxis placebo-controlled trial is recommended to test the impact of prophylactic drugs in pregnancy and to measure the effect on the mother, and the neonate. The drug that proves to be effective as a prophylactic, should be an integral part of ante-natal care along with iron and folic acid as anti-anemic therapy. Moreover, prompt treatment of malaria infection with the appropriate anti-malarial drug, spray of insecticides and the use of insecticide-impregnated bed-nets and curtains for preventing malaria are recommended.