The Association of Human Leukocyte Antigen Genotyping Among Sudanese Patients With Rheumatoid Arthritis: Reference to Ethnicity.

INTRODUCTION:  Human leukocyte antigens (HLA) account for up to one-half of the total genetic contribution to rheumatoid arthritis (RA) risk. The study investigated the association of HLA class II genotyping with RA susceptibility in Sudanese ethnic groups. METHODS:  The DRB1 and DQB1 alleles and haplotypes were determined in 122 RA patients (i.e., Gaalia = 54, Johayna = 24, Baggara = 17, Nile Nubian = 12, and others = 15) and 120 healthy controls of ethnic groups (i.e., Gaalia = 44, Johayna = 11, Baggara = 15, Nile Nubian = 9, and others = 21) using a polymerase chain reaction with sequence-specific primers method. RESULTS: Susceptibility to RA was associated with a high frequency of DRB1*04 (P = 0.04), DRB1*10 (P = 0.04), and DQB1*03 (P = 2.2 x 10-8/Pc = 6.6 x 10-8) between study ethnic groups, while protective effects were shown with DRB1*07 (P = 0.01), DQB1*02 (P = 0.02), and DQB1*06 (P = 2.2 x 10-6/Pc = 6.6 x 10-6), with an inconsistent frequency between study ethnic groups. The HLA haplotypes that were high in frequency among RA ethnic groups and showed susceptibility associations were DRB1*03-DQB1*03, DRB1*04-DQB1*03, DRB1*08-DQB1*03, DRB1*13-DQB1*02, and DRB1*13-DQB1*03 (P = 0.00003/Pc = 0.0003, P = 0.0001/Pc = 0.0001, P = 0.03, P = 0.004/Pc = 0.03, and P = 3.79x10-8/Pc = 3.3x10-9, respectively). On the contrary, DRB1*03-DQB1*02, DRB1*07-DQB1*02, and DRB1*13-DQB1*06 were lower in frequency in the ethnic groups with RA and may confer protection (P = 0.004/Pc = 0.032, P = 0.002/Pc = 0.02, and P = 0.01, respectively). CONCLUSIONS: Our findings indicate an association between HLA-DRB1 and DQB1 genotypes and the susceptibility to RA in the Sudanese population, with a moderate frequency between our ethnic groups.

Factors controlling the effect of praziquantel on liver fibrosis in Schistosoma mansoni-infected patients.

An association study of a cohort of 177 Sudanese patients infected with Schistosoma mansoni [82 (46%) males and 95 (54%) females] was conducted to evaluate the factors controlling the regression of liver fibrosis 39 months after treatment with praziquantel using ultrasound evaluation. Periportal fibrosis (PPF) was regressed in 63 (35.6%) patients, while the disease progressed to higher grades in 24 (13.6%) patients. The grade of PPF did not change in 90 (50.8%) patients. The mean values of portal vein diameter, splenic vein diameter and index liver size in subjects in whom PPF regressed after treatment were significantly lower than in subjects in whom the disease was progressed (P<0.0001, P=0.031 and P=0.003, respectively). The progression of hepatic fibrosis in males (15, 8.5%) was greater than that in females (9, 5.1%). Patients with regression or progression phenotypes tend to cluster in certain families. Our study indicated that regression, progression and stabilization of PPF after praziquantel therapy is controlled by gender, age, grade of fibrosis and possibly inherited factors.

Epidemiology of HCV infection in Gezira state of central Sudan.

This is a cross sectional study carried out in Gezira state of central Sudan, an area with a high prevalence of Schistosoma mansoni infection, to determine the prevalence of hepatitis C virus (HCV) antibodies and risks factors for HCV infection. A total of 410 subjects in Um Zukra village were tested for HCV antibodies, 2.2% were reactive. The prevalence was highest in those between 11 and 20 years old with equal prevalence among males and females. No correlation was found between HCV infection and S. mansoni infection or parenteral antischistosomal therapy. It was concluded that HCV infection is of low seroprevalence and that schistosomiasis and parenteral antischistosomal therapy are not major risk factors for infection in the population studied.

In vitro study assessing the response of plasmodium falciparum malaria to chloroquine, sulfadoxine/pyrimethamine, quinine and mefloquine in Wad Medani District, Sudan.

OBJECTIVE: To assess the in vitro response of Plasmodium falciparum malaria to chloroquine (CQ), sulfadoxine/pyrimethamine (SDX/PYR), Quinine (QU) and Mefloquine (MQ) and monitoring their resistance. METHODS: In 1999 to 2000, an in vitro study was carried out in Wad Medani district in Sudan. The standard protocol of the WHO in vitro micro-test Mark II was used for the selection of the subjects, the collection of blood samples, the culture techniques, the examination of the post-culture blood slides and the interpretation of the results. RESULTS: In vitro micro-test Mark II were performed on 62 Plasmodium falciparum isolates. Of these isolates, 42 produced successful schizonts growth. The data obtained showed that 29 of 42 isolates (69%) were CQ resistant with an effective concentrations (EC); EC50 = 399.621 nM, EC90 = 2754.145 nM and EC99 = 13284.967 nM to inhibit the schizont maturation, the values of SDX/PYR showed a flat regression line as an indication of in vitro reduced response with an EC50 = 0.262 nM, EC90 = 147.390 nM and EC99 = 25722.296 nM, and the response to the QU indicated only one of the 42 isolates (2.4%) was resistant with an EC50 = 150.085 nM, EC90 = 822.825 nM and EC99 = 3293.667 nM, while all the 42 isolates were sensitive to MQ with an EC50 = 190.763 nM, EC90 = 615.125 nM and EC99 = 1597.504 nM. CONCLUSION: The results of this study revealed a high degree of in vitro resistance to CQ and reduced in vitro response to SDX/PYR and QU, while MQ was fully sensitive. The effective concentrations to inhibit 50, 90 and 99% of the parasite maturation were determined for antimalarial drugs efficacy monitoring surveillance in Sudan.

Evaluation of the direct agglutination test based on freeze-dried Leishmania donovani promastigotes for the serodiagnosis of visceral leishmaniasis in Sudanese patients.

The direct agglutination test (DAT) based on freeze-dried (FD) Leishmania donovani antigen was evaluated for the serodiagnosis of kala-azar in a rural setting in eastern Sudan. The performance of the FD-DAT was compared with standard liquid antigen (LQ) by testing serum samples and blood samples collected on filter paper of microscopically and PCR-confirmed VL patients, apparently healthy endemic controls and patients with other relevant infectious diseases for the region. In the present study, the FD-DAT had a sensitivity of 96.8% and a specificity of 96.2%. The LQ-DAT had a sensitivity of 91.0% and a specificity of 96.6%. A high degree of agreement (97.3%; r-value 0.94) was observed between the FD-DAT and the LQ-DAT, as well as between the FD-DAT performed on serum samples and corresponding blood samples collected on filter paper (agreement 97.8%; r-value 0.79). The FD-DAT is very suitable as diagnostic test for kala-azar in remote rural conditions as it is sensitive, specific and stable. The antigen is affordable, reproducible and available, which contributes to the sustainability of the DAT as a diagnostic test for VL.

Cytokine regulation of periportal fibrosis in humans infected with Schistosoma mansoni: IFN-gamma is associated with protection against fibrosis and TNF-alpha with aggravation of disease.

Hepatic periportal fibrosis, which affects 5-10% of subjects infected by Schistosoma mansoni, is caused by the T cell-dependent granuloma that develop around schistosome eggs. Experimental models of infection have shown that granuloma and fibrosis are tightly regulated by cytokines. However, it is unknown why advanced periportal fibrosis occurs only in certain subjects. The goal of the present study was to evaluate the cytokine response of S. mansoni-infected subjects with advanced liver disease in an attempt to relate susceptibility to periportal fibrosis with an abnormal production of cytokines that regulate granuloma and fibrosis. Fibrosis was evaluated by ultrasound on 795 inhabitants of a Sudanese village in which S. mansoni is endemic: advanced periportal fibrosis was observed in 12% of the population; 35% of the affected subjects exhibited signs of portal hypertension. Age (odds ratio (OR), 11.5), gender (OR, 4.2), and infection levels (OR, 2.2) were significantly (p < or = 0.01) associated with hepatic fibrosis. Cytokines produced by egg-stimulated blood mononuclear cells from 99 subjects were measured (75 with no or mild fibrosis; 24 subjects with advanced fibrosis). Multivariate analysis of cytokine levels showed that high IFN-gamma levels were associated with a marked reduction of the risk of fibrosis (p = 0.01; OR, 0.1); in contrast, high TNF-alpha levels were associated with an increased risk (p = 0.05; OR, 4.6) of periportal fibrosis. Moreover, infection levels were negatively associated with IFN-gamma production. These results with observations in experimental models strongly suggest that IFN-gamma plays a key role in the protection of S. mansoni-infected patients against periportal fibrosis, whereas TNF-alpha may aggravate the disease.