Hepatitis C genotype 4: genotypic diversity, epidemiological profile, and clinical relevance of subtypes in Saudi Arabia

Hepatitis C virus genotypes 4 [HCV-4] is the most prevalent genotype in Saudi Arabia, although it's various subtypes, mode and route of transmission remains unknown. The aim of this study was to analyze [i] the variability of the HCV-4 subtypes, the route and source of HCV transmission and [ii] the influence of HCV-4 subtypes on their therapeutic response. Sixty-four HCV-4 patients were analyzed retrospectively for the prevalence of various sub-genotypes and the possible mode of transmission, and it was correlated with their treatment response to pegylated interferon [PEG-IFN] alpha-2a and ribavirin therapy. Positive history of blood or blood products transfusion was noted in 22 patients [34%], hemodialysis in 10 patients [15.6%], surgery in 7 patients [11%], and unknown etiology in 25 patients [39%]. Prevalence of HCV-4 subtypes was 4a = 48.4% [31/64], 4d = 39% [25/64], 4n = 6.25% [4/64], and remaining combined [4m, 4l, 4r, 4o] 6.25% [4/64]. No significant correlation between subtypes and the source of transmission was recognized [P = 0.62]. Sustained virological response in all HCV-4 patients was 64% [41/64], while in each subtypes separately it was 4a 77.4% [24/31], 4d 52% [13/25], and combined [4n, 4m, 4l, 4r, 4o] 62.5% [5/8] [P = 0.046]. No obvious cause for the mode of HCV transmission was noted in majority of the patients. No significant correlation was observed between HCV-4 subtypes and the source of HCV infection. 4a and 4d subtypes were the most common in Saudi Arabia, and patients infected with 4a subtype responded significantly better to combination therapy than to 4d subtype

Analysis of gene mutations involved in chloroquine resistance in Plasmodium faIdparum parasites isolated from patients in the southwest of Saudi Arabia

Chloroquine has been the drug of choice for the treatment of malaria for many decades. We aimed to examine the molecular basis of chloroquine resistance among Plasmodium falciparum isolates from the southwestern region of Saudi Arabia by analyzing the K76T and N86Y mutations in the PfCRT and PfMDR1 genes, respectively. P falciparum-infected blood spot samples [n=121] were collected on filter papers. DMA was extracted and fragments from the above genes were amplified using nested PCR. The amplicons were digested by Apol enzyme and sequenced. Of the 121 samples, 95 and 112 samples could be amplified for PfCRT K76T and PfMDR1 N86Y mutations, respectively. All of the samples amplified for the PfCRT K76T mutation were undigestible by Apol, suggesting the presence of the K76T mutation. For the PfMDR1 N86Y mutation, 65/109 samples [59.6%] were digestible when treated with Apol in a pattern, suggestive of the presence of the investigated wild allele [N86]. However, 44/109 samples [40.4%] were digestible by Apol, suggesting the presence of the mutated allele [Y] at position 86. DMA sequencing confirmed these results. Surprisingly, all isolates exhibited the mutated allele at codon 76 [K76T] of PfCRT. However, the mutated mutant allele at codon 86 [N86Y] of PfMDR1 was found in 40.4% of the samples studied. To our knowledge, this is the first study that has investigated the existence of the mutation in the PfMDR1 gene in the country. This study will contribute to the development of new strategies for therapeutic intervention against malaria in Saudi Arabia

Transmission of hepatitis-B virus through salivary blood group antigens in saliva

To determine an association between transmission of hepatitis B virus and secretor and non-secretor status of salivary blood group antigens. Cross-sectional, analytical study. The Department of Physiology and Division of Hepatology, College of Medicine, King Khalid University Hospital, King Saud University, Riyadh, Kingdom of Saudi Arabia, from 2007 to 2009. Eighty eight known patients, who were positive for Hepatitis B Surface Antigen [HBsAg] were recruited. Saliva was collected for investigating the secretor and non-secretor status by using blood typing kit number Kemtec Educational Science USA. Hepatitis B Surface antigen test was performed on Enzyme Linked Immunosorbent Assay technique. Polymerase chain reaction [PCR] on saliva was also carried out in High Performance Thermal Cycler-Palm-Cycler[TM] [Corbett Life Science, Sydney, Australia] and enzymatic amplification of extracted viral DNA was performed using primers covering the promoter of the core region of HBV. Out of the 88 subjects, 61 belong to blood group O, 20 to A and 7 subjects to blood group B. Fifty subjects were secretors [salivary blood group antigens positive] and 38 subjects were non-secretors [salivary blood group antigens negative]. Among core gene positive 25 [69.4%] were secretors and 11 [30.6%] were non-secretors. However, in core gene negative 25 [48.1%] were secretors and 27 [51.9%] were non-secretors. The result shows an association [p=0.047] between secretor and non-secretors status of the salivary blood group antigens with core gene positive and core gene negative

Inhibition of growth of Leishmania donovani promastigotes by newly synthesized 1,3,4-thiadiazole analogs

Leishmania donovani, the causative agent of visceral leishmaniasis, is transmitted by sand flies and replicates intracellularly in their mammalian host cells. The emergence of drug-resistant strains has hampered efforts to control the spread of the disease worldwide. Forty-four 1, 3, 4-thiadiazole derivatives and related compounds were tested in vitro for possible anti-leishmanial activity against the promastigotes of L. donovani. Micromolar concentrations of these agents were used to study the inhibition of multiplication of L. donovani promastigotes. Seven compounds were identified with potential antigrowth agents of the parasite. Compound 4a was the most active at 50 micro M followed by compound 3a. These compounds could prove useful as a future alternative for the control of visceral leishmaniasis