The Prevalence of Multi-Drug Resistance-1 Gene of Plasmodium Falciparum Malaria in Gezira State-Central Sudan

Abstract:Malaria parasite resistance to chloroquine poses a severe and increasing health problem in tropical countries. Implementing molecular markers for monitoring the drug resistance may be essential to overcome the problem. The aim of the present study is to investigate the prevalence of multi-drug resistance of p. falciparum parasite in malaria patients. Blood samples for DNA extraction were collected from the positive malaria patients. The prevalence of mutations in P. falciparum multi-drug resistant gene-1 (pfmdr-1) was detected by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) methods. Approximately; 74.1 of study populations are adults and 25.9 are children. Regression analysis shows a decrease in malaria incidence with increasing age. The prevalence of malaria is higher in males (58.6) compared to females (41.4). There were no statistical differences between malaria incidence and the socioeconomic level within the study population. The frequency of homozygous N/86 and Y/86 alleles were 51.7 and 37.9; respectively; and the heterozygous N/Y86 allele was 10.3.In conclusion the frequency of Pfmdr-1 N/Y86 allele among P. falciparum multi-drug resistant isolates support the hypothesis that Pfmdr-1 N/Y86 allele could be used as predictive marker to monitor multi-drug susceptibility in epidemiological surveys

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.

IFN-gamma polymorphisms (IFN-gamma +2109 and IFN-gamma +3810) are associated with severe hepatic fibrosis in human hepatic schistosomiasis (Schistosoma mansoni).

Schistosome infection is a major public health concern affecting millions of people living in tropical regions of Africa, Asia, and South America. Schistosomes cause mild clinical symptoms in most subjects, whereas a small proportion of individuals presents severe clinical disease (as periportal fibrosis (PPF)) that may lead to death. Severe PPF results from an abnormal deposition of extracellular matrix proteins in the periportal spaces due to a chronic inflammation triggered by eggs and schistosome Ags. Extracellular matrix protein production is regulated by a number of cytokines, including IFN-gamma. We have now screened putative polymorphic sites within this gene in a population living in an endemic area for Schistosoma mansoni. Two polymorphisms located in the third intron of the IFN-gamma gene are associated with PPF. The IFN-gamma +2109 A/G polymorphism is associated with a higher risk for developing PPF, whereas the IFN-gamma +3810 G/A polymorphism is associated with less PPF. The polymorphisms result in changes in nuclear protein interactions with the intronic regions of the gene, suggesting that they may modify IFN-gamma mRNA expression. These results are consistent with the results of previous studies. Indeed, PPF is controlled by a major locus located on chromosome 6q22-q23, closely linked to the gene encoding the alpha-chain of the IFN-gamma receptor, and low IFN-gamma producers have been shown to have an increased risk of severe PPF. Together, these observations support the view that IFN-gamma expression and subsequent signal transduction play a critical role in the control of PPF in human hepatic schistosome infection (S. mansoni).