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Intervention studies have demonstrated that the n-3 fatty acids, docosahexaenoic and eicosapentaenoic acids, ameliorate seizure frequency in patients with drug-resistant epilepsy (DRE). There is a scarcity of fatty acid status of patients with epilepsy. We have investigated blood fatty acids of patients with DRE and assessed the indices of elongase and desaturase activities. DRE patients (n = 83) and healthy controls (n = 31) were recruited form Soba University Hospital Neurology Referral Clinic and Ibn-Auf paediatric Teaching Hospital Neurology Referral Clinic, Khartoum, Sudan. Fatty acid composition of plasma total lipids, phosphatidylcholine and neutral lipids were analysed. The patients compared with their healthy counterparts had higher levels of C14:0, C16:0, C18:0, C20:0, C22:0 (p0.05) and C24:0, and total saturates (p0.05). Similarly, the proportions of C16:1n-7, 18:1n-7, C18:1n-9, C20:1n-9, C24:1n-9 and total monounsaturated fatty acids; p0.005) were higher in the drug-resistant patients. Conversely, the patients had lower levels of n-6 (C18:2n-6, C18:3n-6, C20:4n-6, n-6 metabolites and total n-6; p0.005 and C20:2n-6 and C20:3n-6; p0.05) and n-3 (C20:5n-3, C22:5n-3, C22:6n-3, ∑EPA and DHA, n-3 metabolites and total n-3; p0.05) fatty acids. Indices of elongase and desaturase activities - The plasma total lipid ratios of C16:0/C14:0 (p = 0.001), C18:0/C16:0 (p = 0.001), C16:1n-7/C16:0 (p = 0.027), C18:1n-9/C18:0 (p = 0.022) and C22:4n-6/C20:4n-6 (p = 0.008) were higher and C18:3n-6/C18:2n-6 (p = 0.05), C20:4n-6/C20:3n-6 (p = 0.032) and C20:4n-6/C18:2n-6 (p0.05) lower in the patients with drug-resistant epilepsy than in the healthy control subjects. DRE is associated with blood fatty acid perturbation and abnormal activities of long-chain fatty acid elongase (ELOVL-6), stearoyl-coenzyme A desaturase-1 (SCD-1), delta 6-fatty acid desaturase (D6D) and delta 5 fatty acid desaturase (D5D). N-3 fatty acids are known to ameliorate seizures frequency and dampen neuronal hyperexcitability. Therefore, patients with DRE should be regularly monitored and, if necessary, supplemented with n-3 fatty acids.

Background Preeclampsia is a global health problem and it is the main cause of maternal and perinatal morbidity and mortality. Breastfeeding has been reported to be associated with lower postpartum blood pressure in women with gestational hypertension. However, there is no published data on the role that breastfeeding might play in preventing preeclampsia. The aim of the current study was to investigate if breastfeeding was associated with preeclampsia in parous women. Method A case-control study was conducted in Saad Abualila Maternity Hospital in Khartoum, Sudan, from May to December 2019. The cases (n = 116) were parous women with preeclampsia. Two consecutive healthy pregnant women served as controls for each case (n = 232). The sociodemographic, medical, and obstetric histories were gathered using a questionnaire. Breastfeeding practices and duration were assessed. Results A total of 98 (84.5%) women with preeclampsia and 216 (93.1%) women in the control group had breastfed their previous children. The unadjusted odds ratio (OR) of preeclampsia (no breastfeeding vs breastfeeding) was 3.55, 95% confidence interval (CI) 1.64,7.70 and p value = 0.001 based on these numbers. After adjusting for age, parity, education level, occupation, history of preeclampsia, history of miscarriage, body mass index groups the adjusted OR was 3.19, 95% CI 1.49, 6.82 (p value = 0.006). Conclusion Breastfeeding might reduce the risk for preeclampsia. Further larger studies are required.

Background Dengue fever (DF) is an arthropod-borne disease caused by dengue virus (DENV). DENV is a member of the genus Flavivirus in the family Flaviviridae. Recently, DENV has been reported as an important emerging infectious viral pathogen in Sudan. Multiple outbreaks and sporadic cases of DF have been frequently reported in the eastern region of Sudan. The present study was conducted to confirm DENV outbreak in Kassala State, eastern Sudan, 2019, and to provide some information on the molecular characterization of the DENV isolate associated with the disease outbreak. Methods A hundred serum samples were collected during the outbreak from residents of Kassala State, Sudan, 2019. ELISA was used to detect DENV non structural protein NS1 (DENV-NS1) in acute phase sera sampled during the disease outbreak. RT-PCR assays were used to amplify a fragment of the capsid/pre-membrane region (CprM) of the viral polyprotein gene. The PCR products of the amplified CprM region of the viral polyprotein gene were purified and partial sequences were generated and used to confirm the specificity of DENV sequences and to identify the virus serotype. Phylogenetic tree was constructed to determine the genotype of DENV associated with the outbreak. Results Using DENV-NS1 ELISA assay, DENV infection was confirmed in 23% sampled sera. The detection of DENV RNA was made possible using group-specific RT-PCR assay. The virus was serotyped as DENV serotype 3 (DENV-3) using DENV serotype-specific RT-PCR assay. Phylogenetic analysis of the partial CprM sequences of the viral polyprotein gene indicates that the virus belonged to genotype III of DENV-3. Conclusion The scientific data presented in this investigation confirmed that genotype III of DENV-3 was associated with the disease outbreak in eastern Sudan, 2019. The study represents the first report on molecular characterization of DENV-3 in Sudan.

A recent symposium and workshop in Khartoum, the capital of the Republic of Sudan, brought together broad expertise from three universities to address the current burden of communicable and non-communicable diseases facing the Sudanese healthcare system. These meetings identified common challenges that impact the burden of diseases in the country, most notably gaps in data and infrastructure which are essential to inform and deliver effective interventions. Non-communicable diseases, including obesity, type 2 diabetes, renal disease and cancer are increasing dramatically, contributing to multimorbidity. At the same time, progress against communicable diseases has been slow, and the burden of chronic and endemic infections remains considerable, with parasitic diseases (such as malaria, leishmaniasis and schistosomiasis) causing substantial morbidity and mortality. Antimicrobial resistance has become a major threat throughout the healthcare system, with an emerging impact on maternal, neonatal and paediatric populations. Meanwhile, malnutrition, micronutrient deficiency and poor perinatal outcomes remain common and contribute to a lifelong burden of disease. These challenges echo the United Nations (UN) sustainable development goals and concentrating on them in a unified strategy will be necessary to address the national burden of disease. At a time when the country is going through societal and political transition, we draw focus on the country and the need for resolution of its healthcare needs.

Summary Objective To investigate the epidemiology of sickle cell disease (SCD) and determinants of knowledge, attitudes and practices (KAP) towards SCD in western Kordofan State, Sudan. Methods A community-based, descriptive, cross-sectional study was conducted in three towns. Three hundred and seventy-two households were polled, and blood samples for haemoglobin phenotyping were collected from 1116 individuals. Sociodemographic, socio-economic and KAP data were collected using investigator-administered questionnaires. Descriptive, frequency distribution and multiple regression analyses were performed. Results About 50.9% of the study population were Misseriya tribes. Consanguineous marriages were reported by 67.5% of the households. The highest percentage of homozygous SCD was 2.8% among children under 5 years of age. About 24.9% were carriers of HbS allele (HbAS). HbS allele frequency was highest in children aged 5–11 years (18.3%, CI: 13.7–22.9%) and lowest in males >15 years old (12.0%, CI: 6.1–17.9%). The average HbS frequency across all age groups was 14.5% (95% CI: 12.2–16.8%). The most frequent β-globin gene cluster haplotype was the Cameroon (30.8%), followed by the Benin (21.8%), the Senegal (12.8%) and the Bantu (2.2%) haplotypes. About 17.0% of all-cause child deaths were due to SCD. The estimated change in log odds of having the SS genotype per year increase in age was (−) 0.0058 (95% CI −0.0359, 0.0242). This represents a non-statistically significant 2.9% increase in 5-year mortality for individuals with the SS genotype relative to those with AS and AA genotypes. About 46.9% of the households had poor knowledge, 26.1% had satisfactory knowledge, and 26.9% had good knowledge about sickle cell disease. Mothers' and fathers' educational levels were significant predictors of good knowledge about SCD (P < 0.05). About 48.0% had a satisfactory attitude towards sickle cell disease while 30.7% had poor attitude and only 21.3 showed good attitudes. Poor knowledge about SCD and low socio-economic status were the strongest positive predictors of poor attitude and practices towards SCD (P < 0.01). Conclusions Sickle cell disease is a major health problem in West Kordofan, Sudan. Knowledge, attitude and practices towards the disease are not satisfactory. The development of public health programs is highly recommended to control and manage SCD in western parts of Sudan.

Objectives The omega-3 (n − 3) fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are known to play an important role in maintenance and modulation of neuronal functions. There is evidence that omega-3 fatty acids may have anticonvulsant effects. The effect of DHA and EPA on seizure rate in patients with drug-resistant epilepsy (DRE) was investigated. Methods A double-blind, randomized, placebo-controlled clinical trial included ninety-nine (n = 99) subjects with DRE, aged 5–16 years (n = 85) and 17–45 years (n = 14). After randomization, subjects were given two, four, or six capsules per day of DHA (417.8 mg DHA and 50.8 mg EPA/capsule, n = 33), EPA (385.6 mg EPA and 81.2 mg DHA/capsule, n = 33), or placebo (high oleic acid sunflower oil, n = 33) for one year. The primary endpoint was the effect of treatment on rate of seizure. Random-effects negative binomial regression models were fitted to model the patients' total count of seizures per month. The treatment effects on seizure incidence rate ratio (IRR) were tested after controlling for the covariate effects of gender, age, rate of seizure per week at enrollment, type of seizure, and number of antiepileptic drug (AED) combinations used at enrollment. Results Fifty-nine subjects (n = 59) completed the study (59.6%). The average number of seizures per month were 9.7 ± 1.2 in the EPA group, 11.7 ± 1.5 in the DHA group, and 16.6 ± 1.5 in the placebo group. Age, gender, and seizure-type adjusted seizure IRRs of the EPA and DHA groups compared with the placebo group were 0.61 (CI = 0.42–0.88, p = 0.008, 42% reduction) and 0.67 (CI = 0.46–1.0, p = 0.04, 39% reduction), respectively. There was no difference in IRR between the EPA and DHA groups (p = 0.56). Both treatment groups had a significantly higher number of seizure-free days compared with the placebo group (p Significance This study demonstrates that EPA and DHA are effective in reducing seizure frequency in patients with DRE.

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.

Background: \ud It has been reported that patients with SCD do have an abnormal coagulation profile. Coagulopathy is thought to be one of the key factors that contribute to the vaso-occlusive crisis that characterises sickle cell disease (SCD). In this study, we investigated whether Sudanese sickle cell patients have an abnormal coagulation profile. In addition, the effect of treatment with either omega-3 fatty acids or hydroxyurea on coagulation profile was assessed.\ud \ud Methods: \ud Homozygous SCD patients untreated (n = 52), omega-3 treated (n = 44), hydroxyurea (HU) treated (n = 8) and healthy (HbAA) controls (n = 52) matched for age (4–20 years), gender and socioeconomic status were enrolled. Patients on omega-3 fatty acids, according to age, received one to four capsules containing 277.8 mg DHA and 39.0 mg eicosapentnoic. Patients on Hydroxyurea were in on dosage more than 20 mg/kg/day. The steady state levels of the coagulation parameters and the effect of the treatments with either HU or omega-3 fatty acids on markers of coagulation were investigated.\ud \ud Results: \ud Compared to the healthy controls, treated and untreated HbSS patients had lower hemoglobin, plasma Protein C, proteins S and higher white blood cell count (WBC), platelets count (PLTs) and plasma D-dimer levels,(p < 0.05). In comparison to untreated HbSS, treatment with neither omega-3 nor HU had effect on the WBC, plasma proteins C and S, (p > 0.05). HU treated group had a lower PLTs count compared to HbSS untreated group (p < 0.5). The prothrombin and activated partial thromboplastin times and international normalized ratio (INR) of untreated patients are significantly higher than n-3 treated, HU-treated patients and health controls, (p < 0.05). Patients treated with omega-3 had lowered D-dimer levels in comparison to HU-treated and untreated HbSS patients, (p < 0.001).\ud \ud Conclusion: \ud This study provides evidence that Sudanese patients have abnormal coagulation profile and treatment with either HU or omega-3 fatty acids might partially ameliorate SCD-associated chronic coagulopathic state. Keywords: Sickle cell disease, Coagulation, Omega-3 fatty acids, D-dimer, Protein C, Protein S

We investigated whether or not Omega-3 long-chain polyunsaturated fatty acid (omega-3 LCPUFA) supplementation exacerbates oxidative stress in homozygous sickle cell patients aged 2 to 14 years. Depending on their age, they received between one and three omega-3 (277.8mg DHA and 39.0mg EPA/capsule) or placebo (high oleic acid sunflower seed oil) capsules for one year. Supplementation increased significantly the levels of the two fatty acids in red cell phosphatidylcholine and phosphatidylethanolamine (p0.001). The patients who received omega-3 LCPUFA compared with their placebo-taking counterparts had a higher concentration of plasma vitamin E at one year (14.3±2.8 versus 12.3±2.8µmol/l; p0.001). The two groups had comparable concentrations of the vitamin at six month intervention (10.8±2.2 versus 10.7±2.9µmol/l; p0.05) and baseline (10.7±3.1 versus 10.7±2.8µmol/l; p0.05). After six month of intervention, the patients on omega 3 fatty acids had lower GPx-1 (33.5±13.4 versus 46.6 ±17.6, p0.01) and Cu/Zn-SOD (1070±600 versus 1470±690 p0.05) activities than at baseline. GPx-1 (33.5±17.6IU/g Hb versus 43.7±13.2IU/g Hb; p0.01) and Cu/Zn-SOD (1070±600IU/g Hb versus 1360±920IU/g Hb; p0.05) activities were reduced in the omega 3 compared with the placebo at six month intervention. There was no difference in the activity of either of the enzymes between baseline and six month intervention in the placebo group (p0.05). This study demonstrates; DHA and EPA supplementation, rather than exacerbating the inherent oxidative stress associated with the disease, seems to provide an antioxidant protection. Hence, it will be safe to provide omega-3 LCPUFA to sickle cell patients to help ameliorate vaso-occlusive and haemolytic crises and membrane fatty acid abnormality.

The pathogenesis of severe Plasmodium falciparum malaria is still obscure, but is believed to be multi-factorial, and among the important factors are intrinsic parasite-properties. Here we investigated the association between clinical manifestation of P. falciparum malaria (an indicator of virulence) and two parasite properties--drug resistance and gametocyte production. Among 996 P. falciparum infections detected in the out-patient clinic of Gedarif Hospital in eastern Sudan, there was no significant association between the incidence of severe versus mild disease and the presence of resistant alleles at the chloroquine-resistance transporter locus (pfcrt-T76) and the multi-drug-resistance locus (pfmdr1-Y86). However, among severe cases, there was a significantly lower prevalence of parasites carrying resistant alleles among patients that died versus survived. There was a trend towards a higher gametocyte rate among severe malaria patients compared with uncomplicated malaria cases. These results are discussed in relation to the fitness of drug resistant parasites.

In Sudanese women with (n = 60) and without (n = 65) pre-eclampsia, circulating lipids, plasma and red cell saturated and monounsaturated fatty (MUFA) acids and dimethyl acetals (DMAs) were investigated. DMAs are an indirect marker of levels of plasmalogens, endogenous antioxidants, which play a critical role in oxidative protection, and cholesterol homeostasis. The pre-eclamptics had higher C18:1n-9 (p < 0.001) and ΣMUFA (p < 0.01) in plasma free fatty acids, C16:1n-7, C18:1n-9, ΣMUFA; 16:0/16:1n-7 (p < 0.01) in erythrocyte choline phosphoglycerides (ePC) and 16:1n-7, 18:1n-7 and 16:0/16:1n-7 (p < 0.01) in erythrocyte ethanolamine phosphoglycerides (ePE). In contrast, the DMAs 18:0, 18:1 and ΣDMAs in ePE, and 16:0, 18:0 and ΣDMAs in ePC were reduced (p < 0.001) in the pre-eclamptic women. This study of pregnant women with high carbohydrate and low fat background diet suggests pre-eclampsia is associated with oxidative stress and enhanced activity of the microsomal enzyme stearyl-CoA desaturase (delta 9 desaturase), as assessed by palmitic/palmitoleic (C16:0/C16:n-1) and stearic/oleic (C18/C18:1n-9) ratios.

BACKGROUND Few data exist concerning pathogenesis of severe malaria in areas of unstable malaria transmission. OBJECTIVES The study was conducted in Senga hospital, central Sudan, which is characterized by unstable malaria transmission to investigate the cytokine profiles in children with severe Plasmodium falciparum malaria. METHODS Enzyme-linked immunosorbent assay was used to measure the concentrations of three cytokines, interferon gamma (IFN-γ), interleukin-4 (IL-4) and IL-10, in sera of three groups of children (31 in each arm): those with one or more manifestations of severe malaria, those children with uncomplicated P. falciparum malaria and healthy controls. RESULTS The levels of both IFN-γ and IL-10 were significantly higher in patients with severe P. falciparum malaria. Medium positive correlations were observed between IFN-γ and IL-10. CONCLUSION Thus, the high levels of both IFN-γ and IL-10 indicated their role in the pathogenesis of severe P. falciparum malaria.

Aim: The suckling neonates and infants are reliant primarily on the mother for optimal supply of docosahexaenoic acid (DHA). The richest source of preformed DHA is cold-water oily fish. Although there is paucity of data, existing evidence suggest women with restricted access to these foods have low or marginal DHA status. The aim of the study was to investigate milk fatty acids of Sudanese mothers whose traditional diet is high in carbohydrate and low in fat and gain some insight into the provision of DHA to the suckling offspring. Methods: Colostrum (n = 26), transitional (n = 20) and mature (n = 14) milk samples were obtained from Northern Sudanese women (NSW) recruited prior to delivery from Ibrahim Malik and Khartoum Teaching Hospitals. Results: The arachidonic acid content of the colostrum (0.87 ± 0.28%) and transitional (0.89 ± 0.29%) and mature (0.48 ± 0.12%) milk of the NSW were broadly comparable with published international values. In contrast, the DHA level (colostrum 0.13 ± 0.07%, transitional 0.13 ± 0.06% and mature milk 0.06 ± 0.05%) was very low. Conclusion: The study reveals breast milk of NSW, whose traditional diet is almost devoid of fish and fish products, is unlikely to provide sufficient DHA to support optimal postnatal neuro-visual development.

A case-control study was conducted in Khartoum hospital, Sudan to compare omega-3 and omega-6 fatty acids profile in three phospholipid fractions (phosphatidylethanolamine, phosphatidylcholine and sphingomyelin) using gas chromatography in erythrocytes from 65 pre-eclamptic women and well-matched 60 healthy control pregnant women, both in the third trimester of pregnancy. While levels of arachidonic acid (omega-6 fatty acid) was significantly higher in women with pre-eclampsia in the sphingomyelin fraction only, the levels of eicosapentaenoic and docosahexaenoic acid (omega-3 fatty acid) in the three phospholipids fractions were significantly higher in women with pre-eclampsia than in the control group. Both omega-3 and omega-6 fatty acids profiles were not significantly different between patients with mild (diastolic blood pressure (DBP)110 mmHg) and severe (DBPor = 110 mmHg) pre-eclampsia.

Anaemia is a widespread problem especially in the tropics. Among adolescent girls, it has negative consequences on growth, school performance, morbidity and reproductive performance. A cross-sectional study was conducted to investigate the prevalence of anaemia, iron, folate, zinc and copper deficiencies amongst adolescent schoolgirls in New Halfa, eastern Sudan, and to examine the relationship of these micronutrients with haemoglobin (Hb) levels. Out of 187 adolescent schoolgirls, 181 (96.8%) had anaemia (Hb

Background. Cytokine imbalance in preeclampsia may be one of the etiological factors for preeclampsia. Objectives. The study was conducted to investigate interferon gamma (IFN-γ), interleukin-4 (IL-4) and interleukin-10 (IL-10) in preeclampsia. Enzyme-linked immunosorbent assay (ELISA) was used to measure the concentrations of these three pro-inflammatory cytokines in sera from 33 Sudanese women with preeclampsia (at presentation and 7 days later) and 32 women with normal pregnancy as a control group. Results. The levels of IFN-γ and IL-4 were slightly—not statistically significant— higher in the women with preeclampsia. IL-10 was significantly higher in the women with preeclampsia. Women with preeclampsia had significantly lower levels of IFN-γ and IL-4 and significantly higher levels of IL-10 7days later in comparison with the presenting levels. Conclusion. Thus, the significantly raised levels of IL-10 in women with preeclampsia suggest its role in pathogenesis of preeclampsia, and further research is ...

Despite many intervention programmes aimed at curtailing the scourge, malaria remains a formidable problem of human health. Immunity to asexual blood-stage of Plasmodium falciparum malaria is thought to be associated with protective antibodies of certain immunoglobulin classes and subclasses. We have analysed immunoglobulin G profiles to six leading blood-stage antigens in relation to clinical malaria outcome in a hospital-based study in Sudan. Our results revealed a linear association with anti-AMA-1-IgG1 antibodies in children5 years and reduced risk of severe malaria, while the responses of the IgG3 antibodies against MSP-2, MSP-3, GLURP in individuals above 5 years were bi-modal. A dominance of IgG3 antibodies in5 years was also observed. In the final combined model, the highest levels of IgG1 antibodies to AMA-1, GLURP-R0, and the highest levels of IgG3 antibodies to 3D7 MSP-2 were independently associated with protection from clinical malaria. The study provides further support for the potential importance of the studied merozoite vaccine candidate antigens as targets for parasite neutralizing antibody responses of the IgG1 and IgG3 subclasses.

Summary Background: Understanding the cytokine interactions that underlie both control and disease should be helpful when investigating the pathogenesis of malaria during pregnancy. Few data exists concerning pathogenesis of malaria during pregnancy in areas of unstable malaria transmission. Objectives: The study was conducted in New Halfa hospital, eastern Sudan, which is characterized by unstable malaria transmission to investigate the cytokine profiles in peripheral, placental and cord blood in parturient women. Methods: Enzyme-linked immunosorbent assay was used to measure the concentrations of three cytokines, interferon-c (IFN-c), interleukin-4 (IL-4) and IL-10, in sera from peripheral, placental and cord blood of 87 Sudanese women. Results: The concentrations of these cytokines were significantly higher in peripheral, placental sera from uninfected women than in sera from infected women. IFN-c concentrations were significantly lower in the cord sera from uninfected women in comparison to the infected ones. The levels of these cytokines were not significantly different between the primiparae and multipare. Cord sera in all groups showed lower levels of these cytokines. Strong positive correlations were observed between peripheral and placental cytokines. Conclusion: The immune responses that occur in placental, peripheral and cord blood were influenced by the malaria infections, irrespective of the parity. The immune response during Plasmodium falciparum infection is not different in the peripheral and placental compartments, further studies are required.

Estimation of the prevalence of the molecular markers of sulfadoxine/pyrimethamine (SP) and chloroquine (CQ) resistance and validation of the association of mutations with resistance in different settings is needed for local policy guidance and for contributing to a global map for anti-malarial drug resistance. In this study, malaria patients treated with SP alone (60) and SP with CQ (194) had a total treatment failure (TF) of 35.4%, with no difference between the two arms. The polymerase chain reaction-enzyme-linked immunosorbent assay (PCR-ELISA) method was used to identify polymorphisms in 15 loci in the dhfr, dhps and pfcrt genes in a subset of 168 infections. The results revealed a similar frequency of all single nucleotide polymorphisms (SNPs) in the two arms, except dhps 581G, which was over-represented in infections that failed to respond to SP alone (TF). In all infections, a high frequency of dhfr CICNI haplotype (51I and 108N) was found, but without discrimination between the adequate clinical and parasitological response (ACPR, 75.6%) and TF (82.9%). Similarly, the dhps SGEAA haplotype (437G and 540E) (ACPR, 60.5%; TF, 65.9%) and the combined CICNI/SGEAA haplotype (ACPR, 50%; TF 55%) were not associated with TF. In contrast to other studies in Africa, the triple 51I/59R/108N mutation was rare (0.6%). In addition, the pfcrt CVIET haplotype (93%) was found to be associated with the CICNI/SGEAA haplotype. Finally, these data represent a baseline for SP resistance molecular markers needed before the deployment of SP/artesunate combination therapy in the Sudan.

In this study we intended to examine the extent of genetic diversity of Plasmodium falciparum parasites causing severe malaria (SM). For this purpose, 100 parasite isolates were obtained from patients with SM and uncomplicated malaria, from an area of low and unstable malaria transmission in Sudan. The diversity of infection (DOI) was estimated by relating the number of the different parasite genotypes that were detected to the total number of parasites that were genotyped (parasite population/subpopulation). We used different molecular markers individually (pfcrt-76, pfmr1-86, GLURP size and MSP2 family and size) and as a group to set a multilocus genetic profile for each parasite isolate. The DOI as estimated by MSP2 and GLURP was 0.553 and 0.435, respectively. However, combination of all four molecular markers (multilocus genetic profile) revealed a fingerprint pattern of genetic diversity with a DOI of 0.936, indicating that in SM infection, diversity is the rule and homogeny is the exception. Furthermore, our clinical data suggest that the virulence markers might also be more diverse than expected. In conclusion, the results are unexpected and overturn the assumption that parasites causing SM are a limited subpopulation of virulent parasites or of a clonal nature. However, it was more likely that there was a genetically unique parasite in each infection.

The variant surface antigens (VSA) of infected erythrocytes are important pathogenic markers, a set of variants (VSA(SM)), were assumed to be associated with severe malaria (SM), while SM constitutes clinically diverse forms, such as, severe malarial anemia (SMA) and cerebral malaria (CM). This study was conducted in Eastern Sudan, an area of seasonal and unstable malaria transmission. Parasites and plasma were obtained from patients with different clinical grades of malaria, and flow cytometry was used for analysis of VSA antibody (Ab) response. We found that individuals recognized a broader range of isolates had a higher level of VSA Ab against the recognized isolates (correlation coefficient, 0.727, P

The prevalence and possible risk factors for anaemia were investigated in 744 pregnant Sudanese women attending the antenatal clinic of New Halfa teaching hospital, eastern Sudan between October 2003 and April 2004. Of those, 466 (62.6%) had anaemia (haemoglobin [Hb]

A prospective clinical study in eastern Sudan described the efficacy and toxicity of quinine in early pregnancy in mothers with chloroquine-resistant falciparum malaria. Twenty-six pregnant Sudanese women in their first trimester [mean gestational age 8.5 weeks] were given quinine 10 mg/kg 3 times per day for 7 days and followed up every 2 weeks until delivery. One patient aborted [3.8%] and 2 patients [7.7%] experienced threatened abortion but delivered term babies. Recrudescence or re-infection was observed on day 21 in 1 patient. One baby died aged 6 months. There were no detectable congenital malformations, no auditory or visual defects or any other neurological deficits in the remaining infants at birth or 1 year later. Quinine may be safe in the first trimester of pregnancy

This study was carried in New Halfa Hospital, eastern Sudan from October 1997 to February 2001. Twenty-eight pregnant Sudanese women infected with Plasmodium falciparum were treated with intramuscular artemether (six injections, 480 mg) after failure of chloroquine and quinine therapy. The patients were followed-up until delivery; the babies were followed-up until the age of 1 year. Artemether was given to one patient in the tenth week of gestation, to 12 during the second trimester, and to 15 during the third trimester. It was well tolerated, the parasitaemia was cleared and the patients were symptom-free within three days. One patient (3.5%) delivered at 32 weeks and the baby died six hours after delivery. The other 27 (96.5%) delivered full-term live babies. None of the pregnant women died and there was no abortion, stillbirth or congenital abnormalities in the newborn babies.

A prospective study was carried out in an area of unstable malaria transmission in central Sudan to determine the efficacy and toxicity of quinine in pregnancy. Thirty-three pregnant women with severe Plasmodium falciparum malaria at mean 28.8 weeks gestational age were treated with quinine for 7 days. The mean body temperature on presentation for 3 patients who delivered prematurely was significantly higher than for those who delivered at term [39.2 +/- 0.7 degrees C versus 38.7 +/- 1.3 degrees C]. There were no significant difference between the 2 groups in other clinical or biochemical parameters. There were no clinically detectable congenital malformations and no auditory, visual or other neurological deficits in the babies at birth or 6 months later. Quinine may be safe in the treatment of severe falciparum malaria during pregnancy

A 1-year prospective community-based study of malaria during pregnancy was conducted in an area of seasonal and unstable malaria transmission in eastern Sudan. At a village antenatal clinic, 89 non-pregnant controls and 86 pregnant women were enrolled and followed every 2 weeks until 6 weeks after delivery. The incidence of Plasmodium falciparum infection was significantly higher among pregnant than control women [17.4% versus 5.6%] with no difference between primigravidae and multigravidae [22.2% versus 15.2%]. There was no significant difference in the mean haemoglobin concentration between infected and uninfected mothers [9.1 +/- 1.3 versus 9.5 +/- 0.6 g/dL] but the mean birth weight of their babies was significantly lower [2.72 +/- 0.26 versus 2.95 +/- 0.05 kg] despite prompt case management of infected women

We have earlier indicated neutrophil activation in severe malaria by measuring myeloperoxidase (MPO) and lysozyme, leukocyte granule proteins secreted by neutrophils as well as by other blood cells (monocytes/macrophages). In this study we evaluated the plasma levels of human neutrophil lipocalin (HNL), a specific neutrophil granule protein, in relation to previously reported markers MPO and lysozyme, for clinical significance in indicating severe malaria. For this purpose, plasma samples were analyzed from 65 individuals with severe malaria, mild malaria or malaria negative, all living in the Gedarif area of Sudan. The plasma levels of HNL were significantly higher in the group of patients with severe malaria as compared with the other two groups. Plasma levels of HNL correlated significantly to those of MPO and lysozyme, as well as to body temperature, degree of parasitaemia and pulse rate. These results confirm our previous findings that neutrophils are activated in-patients with severe malaria and the level of HNL is a good marker in this context.

A case–control study was carried out in Kassala and Medani Maternity Hospitals in Sudan to investigate acute-phase proteins [haptoglobin, C-reactive protein (CRP), ferritin and albumin] in three groups of pregnant women (32 in each arm) comprising those with severe Plasmodium falciparum malaria or uncomplicated P. falciparum malaria and healthy controls. Whilst there was no significant difference in the levels of albumin and haptoglobin, ferritin and CRP levels were significantly higher in pregnant women with severe P. falciparum malaria. There were significant positive correlations between parasite count and haptoglobin, and medium positive correlations between parasite count and CRP.

Chronic inflammation and reduced blood levels of omega-3 fatty acids (n − 3) are known characteristics of sickle cell disease (SCD).The anti-inflammatory properties of n − 3 fatty acids are well recognized.\ud \ud Omega-3 treated (n = 24), hydroxyurea (HU) treated (n = 18), and n − 3 untreated (n = 21) homozygous SCD patients (HbSS) and healthy (HbAA) controls (n = 25) matched for age (5–16 years), gender and socioeconomic status were studied. According to age (5–10) or (11–16) years, two or three capsules containing 277.8 mg docosahexaenoic (DHA) and 39.0 mg eicosapentaenoic (EPA) or high oleic acid placebo (41%) were assigned to n − 3 treated and n − 3 untreated groups, respectively. Hydroxyurea treated group was on dosage more than 20 mg/kg/day. The effect of supplementation on systemic and blood cell markers of inflammation was investigated.\ud \ud The n − 3 treated group had higher levels of DHA and EPA (p < 0.001) and lower white blood cell count and monocyte integrin (p < 0.05) compared with the n − 3 untreated. No difference was detected between the two groups regarding C-reactive protein, granulocytes integrin and selectin, plasma tumour necrosis factor-α and interleukin-10. The n − 3 treated group had lowered nuclear factor-kappa B (NF-κB) gene expression compared to n − 3 untreated and HU treated groups (p < 0.05).\ud \ud This study provides evidence that supplementation with n − 3 fatty acids may ameliorate inflammation and blood cell adhesion in patients with SCD.

Background: There are few published data on the association between leptin, insulin like growth factor-1 (IGF-1) and malaria during pregnancy. This study aimed to investigate maternal and umbilical cord leptin and IGF-1 levels and malaria during pregnancy, and their association - if any - with birth weight.Methods: A cross-sectional study was conducted at Medani, Sudan. Medical and obstetrics history was gathered from each parturient woman (n=175) and malaria was investigated by blood film and placental histology. Maternal and umbilical cord leptin and IGF-1 levels were measured using ELISA.Results: Upon histological examination, 48 women were infected with placental malaria, and 127 were found free from the disease. Out of the 48, 2 of the patients showed signs of active infection, 3 of chronic infection and 43 of previous infection. Placental malaria and preterm delivery were associated with low birth weight (< 2500 g). Younger mothers and primigravidae had a higher risk for placental malaria infection. There was no significant difference in maternal and umbilical cord leptin and IGF-1 levels between women infected with placental malaria and those free from the disease.Conclusions: The current study showed that low birth weight was significantly associated with placental malaria. Young mothers and primigravidae had a higher risk to develop the infection. There was no significant difference in the levels of maternal and umbilical cord leptin and IGF-1 levels between women infected with placental malaria and those free from the disease. Both the levels of maternal and cord leptin and IGF-1were found not to be associated with birth weight.Abbreviations: IGF-1: Insulin like growth factor-1; LBW: Low birth weight; ELISA: Enzyme-linked immunosorbent assay; PM: Placental malaria.

Viral sequences analyzed indicate recent virus movement and support the need for surveillance., To elucidate whether Rift Valley fever virus (RVFV) diversity in Sudan resulted from multiple introductions or from acquired changes over time from 1 introduction event, we generated complete genome sequences from RVFV strains detected during the 2007 and 2010 outbreaks. Phylogenetic analyses of small, medium, and large RNA segment sequences indicated several genetic RVFV variants were circulating in Sudan, which all grouped into Kenya-1 or Kenya-2 sublineages from the 2006–2008 eastern Africa epizootic. Bayesian analysis of sequence differences estimated that diversity among the 2007 and 2010 Sudan RVFV variants shared a most recent common ancestor circa 1996. The data suggest multiple introductions of RVFV into Sudan as part of sweeping epizootics from eastern Africa. The sequences indicate recent movement of RVFV and support the need for surveillance to recognize when and where RVFV circulates between epidemics, which can make data from prediction tools easier to interpret and preventive measures easier to direct toward high-risk areas.

Background: Blood cell aggregation and adherence to vascular endothelium and inflammation play a central role in vaso-occlusive crisis in sickle cell disease. The antiaggregatory, antiadhesive, antiinflammatory, and vasodilatory omega-3 (n23) fatty acids (DHA and EPA) are significantly reduced in patients with the disease. Objective: The aim was to investigate the therapeutic potential of omega-3 fatty acids for patients with homozygous sickle cell disease in a randomized, placebo-controlled, double-blind trial. Design: One hundred forty patients recruited from a single center in Sudan were randomly assigned and received, daily, 1 (age 2‐4 y), 2 (age 5‐10 y), 3 (age 11‐16 y), or 4 (age $17 y) omega-3 capsules containing 277.8 mg DHA and 39.0 mg EPA or placebo for 1 y. Of these patients, 128 were followed up and the data were obtained. The primary and secondary endpoints—rates of clinical vaso-occlusive crisis and hemolytic events, blood transfusion rate, school attendance, and blood count—were analyzed by intention-to-treat analysis (n = 140). Results: Omega-3 treatment reduced the median rate of clinical vaso-occlusive events (0 compared with 1.0 per year, P , 0.0001), severe anemia (3.2% compared with 16.4%; P , 0.05), blood transfusion (4.5% compared with 16.4%; P , 0.05), white blood cell count (14.4 6 3.3 compared with 15.6 6 4.0 310 3 /mL; P , 0.05), and the OR of the inability to attend school at least once during the study period because of illness related to the disease to 0.4 (95% CI: 0.2, 0.9; P , 0.05). Conclusion: The findings of this trial, which need to be verified in a large multicenter study, suggest that omega-3 fatty acids can be an effective, safe, and affordable therapy for sickle cell anemia. This trial was registered with Current Controlled Trials as ISRCTN80844630. Am J Clin Nutr 2013;97:37‐44.

Crimean-Congo hemorrhagic fever (CCHF) virus (CCHFV) activity has been detected in Kordufan region of the Sudan in 2008 with high case-fatality rates in villages and rural hospitals in the region. Therefore, in the present study, a reverse transcription (RT) loop-mediated isothermal amplification (RT-LAMP) assay was developed and compared to nested RT-PCR for rapid detection of CCHFV targeting the small (S) RNA segment. A set of RT-LAMP primers, designed from a highly conserved region of the S segment of the viral genome, was employed to identify all the Sudanese CCHFV strains. The sensitivity studies indicated that the RT-LAMP detected 10 fg of CCHFV RNA as determined by naked eye turbidity read out, which is more likely the way it would be read in a resource-poor setting. This level of sensitivity is good enough to detect most acute cases. Using agarose gel electrophoresis, the RT-LAMP assay detected as little as 0.1 fg of viral RNA (equivalent to 50 viral particle). There was 100% agreement between results of the RT-LAMP and the nested PCR when testing 10-fold serial dilution of CCHFV RNA. The specificity studies indicated that there was no cross-reactivity with other related hemorrhagic fever viruses circulating in Sudan including, Rift Valley fever virus (RVFV), Dengue fever virus, and yellow fever virus. The RT-LAMP was performed under isothermal conditions at 63 °C and no special apparatus was needed, which rendered the assay more economical and practical than real-time PCR in such developing countries, like Sudan. In addition, the RT-LAMP provides a valuable tool for rapid detection and differentiation of CCHFV during an outbreak of the disease in remote areas and in rural hospitals with resource-poor settings.

The interaction between iron level, iron supplementation, and susceptibility to infection, including malaria, remains a concern. A cross-sectional study was conducted at Medani hospital in central Sudan to investigate the relationship between anaemia and placental malaria. Obstetrical history was obtained; haemoglobin levels were determined. Placental tissue was obtained and malaria histology classified as active, chronic, past or no malaria infection. Among 324 women investigated, 7 (2.2%), 4 (1.2%), and 44 (13.6%) of the placentae showed active, chronic and past infection on histology examination respectively, while 269 (83.0%) of them showed no infection. Anaemia (haemoglobin

Background Blood platelet levels are being evaluated as predictive and prognostic indicators of the severity of malaria infections in humans. However, there are few studies on platelets and Plasmodium falciparum malaria during pregnancy. Methods A case–control study was conducted at Gadarif Hospital in Eastern Sudan, an area characterized by unstable malaria transmission. The aim of the study was to investigate thrombocytopenia in pregnant women with P. falciparum malaria (cases) and healthy pregnant women (controls). Results The median (interquartile) platelet counts were significantly lower in patients with malaria (N = 60) than in the controls (N = 60), 61, 000 (43,000–85,000) vs. 249,000 (204,000–300,000)/μL, respectively, p P. falciparum malaria (N = 12) compared with those patients with uncomplicated P. falciparum malaria (N = 48), 68, 000 (33,000-88,000)/μL vs. 61, 000 (45,000–85,000)/μL, respectively, p = 0.8. While none of the control group had thrombocytopenia (platelet count p P. falciparum malaria, compared with the pregnant healthy control group, were at higher risk (OR = 10.1, 95% CI = 4.1–25.18; p Conclusion P. falciparum malaria is associated with thrombocytopenia in pregnant women in this setting. More research is needed.

Background Placental malaria and pre-eclampsia occur frequently in women in tropics and are leading causes of maternal and perinatal morbidities and mortality. Few data exist concerning the interaction between placental malaria and pre-eclampsia. Methods A case control study was conducted in Medani Hospital, which locates in an area of unstable malaria transmission in Central Sudan. Case (N = 143) were women with pre-eclampsia, which was defined as systolic blood presure≥140 mm Hg or diastolic blood pressure ≥ 90 mm Hg and proteinuria. Controls were parturient women (N = 143) without any blood pressure values > 139/89 mm Hg or proteinuria. Obstetrical and medical characteristics were gathered from both groups through structured questionnaires. Placental histopathology examinations for malaria were performed. Results Twenty-eight (19.6%) vs. 16 (11.2%); P = 0.04 of the cases vs. controls, had placental malaria infections. Five (2%), 1 (2%) and 22 (28.0%) vs. 1, 2 and 13 of the placentae showed acute, chronic and past infection on histopathology examination in the two groups respectively, while 115 (80.4%) vs.127 (88.8%) of them showed no infection, P = 0.04. In multivariate analysis, while there were no associations between age, parity, educational level, lack of antenatal care, blood groups and body mass index and pre-eclampsia; family history of hypertension and placental malaria (OR = 2.3, 95% CI = 1.0-5.2; P = 0.04) were significantly associated with pre-eclampsia. Conclusion Placental malaria was associated with pre-eclampsia. Further research is needed.

The cytotoxic compound hydroxyurea (HU) is effective therapy for sickle cell disease. However, its effect on unsaturated membrane lipids is unknown. Red cell fatty acids were investigated in HU-treated (n=19) and HU-untreated (n=17) sickle cell patients and controls (n=20). The HU-treated compared with the HU-untreated patients had lower arachidonic (AA) acid level in ethanolamine, physphoglycerids (EPG) (22.9±1.2 versus 24.0±1.1%, P<0.05) serine SPG (22.13±2.2 versus 24.9±2.3%, P<0.01) phosphoglycerides. The treated patients and controls had comparable levels of docosahexaenoic (DHA) and total n-3 fatty acids in EPG and choline phosphoglycerides (CPG). In contrast, the untreated group had significantly (P<0.05) lower DHA and total n-3 compared with the controls in EPG (2.7±0.4 versus 3.2±0.6%and4.6±0.5 versus 5.2±0.7%) and CPG (0.7±0.2 versus 1.0±0.2%and1.2±0.2 versus 1.4±0.3). HU is known to activate cytosolic phospholipase A2 and cyclooxygenase 2, and from this study, it appears to induce mobilisation of AA from the inner cell membrane EPG and SPG. Hence, eicosanoids generated from the released AA may play a role in clinical improvements which occur in HU-treated patients.