Distribution of sand flies in El-Nekheil province,in Al-Madinah Al-Munawwarah region,western of Saudi Arabia

An entomological survey for sand flies was conducted at an area of cutaneous leishmaniasis—El-Nekheil in Northeast Al-Madinah Al-Munawwarah, Saudi Arabia. Standardized sampling with Centers for Disease Control (CDC) light traps and sticky traps was employed to determine monthly trends in species composition, density, sex ratio, and reproductive status and Leishmania infection rate of vector sand flies. A total of 621 sand flies were collected from March 2006 to November 2007. Six species representing two genera were identified, three Phlebotomus species: P. papatasi, P. sergenti, and P. bergeroti; and three Sergentomyia species: S. antennata, S. sergenti, and S. shewtzi. Phlebotomus papatasi was the predominant anthropophagic species found and comprised more than 70% of the sand fly population. A population peak (June) was observed for this species. The density of P. papatasi intra-domiciliary was higher than extra-domiciliary stations and inflated by a greater proportion of female flies. Of 189 dissected Phlebotomus females, 43% were blood-fed. No Leishmania parasites were found. The proportion of gravid P. papatasi increased progressively during the 5-month period from May to September and averaged 38%. Proportions of gravid flies may be a valid indicator of the physiological age and epidemiologic importance of the vector sand fly population at this focus.     

Hepatitis B virus in Gizan, Saudi Arabia

The enzyme-linked immunosorbent assay (ELISA) was used to study the prevalence rates for hepatitis B virus surface antigen (HBsAg), antibody to surface antigen (anti-HBs), and antibody to core antigen (anti-HBc) in 724 voluntary donors, students, pregnant women and those seeking treatment for minor ailments in the Gizan area of Saudi Arabia. Tests for hepatitis B e antigen (HBeAg) and e antibody (anti-HBe) were made in HBsAg positive sera. There was serological evidence of an existing or earlier infection in 337 Saudis (46.5%), of whom 12.7% were HBsAg carriers, 25.4% were positive for anti-HBs, and 8.4% were positive only for anti-HBc. The percentage of HBsAg carriers was 19.9% and 9.3% in males and females, respectively (p less than 0.001). The evidence of existing or earlier infection in males (58.7%) was significantly higher than in females (38.7%) (p less than 0.001), with no intersex difference in anti-HBs or anti-HBc. No difference was observed in the positivity of either of the markers, alone or together, between the cord blood and the female population in the child-bearing age of 20-39 years. Corresponding to the values in other age groups, there was an overall fall in the number of HBsAg carriers during adolescence as well as in 20-39-year-old females. Among the HBsAg carriers, there was no significant difference between the two sexes for HBeAg and anti-HBe positivity. The HBsAg carrier rate of 19.9% in males is consistent with the high male dominant prevalence of hepatocellular carcinoma in the Gizan area.(ABSTRACT TRUNCATED AT 250 WORDS)     

A case of unilocular hydatid disease imported from Saudi Arabia

A 39-year-old Korean man with general malaise was found to have two hepatic cysts by computed tomography. He had the history of close contact with domesticated wild dog in Saudi Arabia in 1976. Two cysts, 15cm and 10cm in diameter which contained clear fluid, were excised from both lobes of the liver. He was pathologically diagnosed as unilocular hydatid disease. This case is regarded as an imported case from Saudi Arabia.     

Molecular characterization of Joubert syndrome in Saudi Arabia

Joubert syndrome (JS) is a ciliopathy that is defined primarily by typical cerebellar structural and ocular motility defects. The genetic heterogeneity of this condition is significant with 16 genes identified to date. We have used a combination of autozygome‐guided candidate gene mutation analysis and exome sequencing to identify the causative mutation in a series of 12 families. The autozygome approach identified mutations in RPGRIP1L, AHI1, TMEM237, and CEP290, while exome sequencing revealed families with truncating mutations in TCTN1 and C5ORF42. Our study, the largest comprehensive molecular series on JS, provides independent confirmation of the recently reported TCTN1, TMEM237, and C5ORF42 as bona fide JS disease genes, and expands the allelic heterogeneity of this disease. Hum Mutat 33:1423–1428, 2012. © 2012 Wiley Periodicals, Inc.     

ICF Syndrome in Saudi Arabia: Immunological, Cytogenetic and Molecular Analysis

Background

Immunodeficiency, centromeric instability and facial anomalies (ICF) syndrome is an extremely rare autosomal recessive disorder. In addition to the juxtacentromeric heterochromatic instability, the disease is characterized by variable reduction in serum immunoglobulin levels which cause most ICF patients to succumb to infectious diseases before adulthood as well as exhibit facial dysmorphism including hypertelorism, epicanthal folds, and low-set ears.

Subjects and Methods

A case series of five patients with ICF from a major immunodeficiency center in Saudi Arabia were included. Immunological and cytogenetic studies were performed for all the five patients. Molecular data was conducted on three patients.

Results

All patients had variable hypogammaglobulinemia and characteristic centromeric instability of chromosomes 1, 16, and sometimes 9. One of the patients had pseudomonas meningitis. Pauciarticular arthritis was noted in one patient, a previously not reported finding in ICF, though it has been reported among patients with humoral immune defect. In addition, we identified a novel homozygous c.2506 G>A (p.V836M) mutation in DNMT3B in one of the three patients tested.

Conclusions

This report describes five patients with ICF Saudi Arabia for the first time. ICF should be suspected in children with facial dysmorphism who present with recurrent infections especially in highly inbred populations.     

Molecular characterization and phylogenetic analysis of human parainfluenza virus type 3 isolated from Saudi Arabia

Human parainfluenza virus 3 (HPIV-3) is a leading cause of respiratory disease in children worldwide. Previous sequence analyses of the entire virus genome, among different HPIV-3 strains, demonstrated that HN is the most variable gene. There is a dearth of data on HPIV-3 strains circulating in Saudi Arabia. In this report, HPIV-3 was screened in nasopharyngeal aspirates collected from hospitalized children with acute respiratory disease during two successive seasons (2007/08 and 2008/09) using nested RT-PCR. Out of 73 samples collected during 2007/08, seven (9.59%) were positive; while 3 out of 107 samples collected during 2008/09 (2.8%) were positive. Virus isolation in cell culture was successful using HEp2, but not Vero cells. The identity of the isolated viruses was confirmed using immunofluorescence and neutralization assays. To elucidate the genetic characteristics and phylogeny of Saudi HPIV-3 strains, the complete HN gene sequence of two selected Saudi strains was analyzed in comparison to 20 strains isolated by others from different countries worldwide. Both strains showed the highest degree of sequence homology with Indian strains, followed by Chinese and most Japanese strains. Phylogenetic analysis confirmed that these strains fell into a distinct Asian lineage. This study is the first in Saudi Arabia to recover HPIV-3 isolates of confirmed identity, and to generate sequence data that may help in understanding virus diversity and evolution.     

Incidence and seroprevalence of dengue virus infections in Australian travellers to Asia

The purpose of this study was to estimate the incidence density and prevalence of dengue virus infection in Australian travellers to Asia. We conducted a multi-centre prospective cohort study of Australian travellers over a 32-month period. We recruited 467 travellers (≥ 16 years of age) from three travel clinics who intended to travel Asia, and 387 (82.9%) of those travellers completed questionnaires and provide samples pre- and post-travel for serological testing for dengue virus infection. Demographic data, destination countries and history of vaccinations and flavivirus infections were obtained. Serological testing for dengue IgG and IgM by enzyme-linked immunosorbent assay (ELISA) (PanBio assay) was performed. Acute seroconversion for dengue infection was demonstrated in 1.0% of travellers, representing an incidence of 3.4 infections per 10,000 days of travel (95% confidence interval [CI]: 0.9-8.7). The seroprevalence of dengue infection was 4.4% and a greater number of prior trips to Asia was a predictor for dengue seroprevalence (p = 0.019). All travellers experienced subclinical dengue infections and had travelled to India (n = 3) and China (n = 1). This significant attack rate of dengue infection can be used to advise prospective travellers to dengue-endemic countries.     

Hepatitis E virus infection in haemodialysis patients: a case-control study in Saudi Arabia.

To determine the prevalence of antibody to hepatitis E virus (IgM anti-HEV) among haemodialysis patients and evaluate whether there was an increased risk of infection and exposure to HEV in an area of endemic viral hepatitis, serum samples obtained from 83 Saudi patients on chronic haemodialysis (group 1), 400 sex- and age-matched healthy subjects (group 2) and hospital patients (group 3) were tested for the IgM anti-HEV and IgG anti-HEV. The prevalence of anti-HEV among the patients (group 1) and the healthy controls were 4.8% and 0.3%, respectively. The difference (4.5%) was statistically significant, with a calculated odds ratio (OR) of 20.2 (95% CI = 2.1-481.0; P = 0.0002). In contrast, there was no significant difference in the prevalence rates of IgG anti-HEV (7.2% vs 10.8%) in both groups. In nonhaemodialysis patients with various diseases, 1.6% (1 of 64) of outpatients (group 3) and none (0 of 113) of the ward patients (group 4) was positive for IgM anti-HEV. Thus, the prevalence (4 of 83) of IgM anti-HEV in the haemodialysis patients was significantly higher than the rate (1 of 177) in the combined groups of nonhaemodialysis hospital patients. The calculated OR was 8.9 (95% CI = 0.92, 212.8; P = 0.037). IgM antibody to hepatitis A virus (IgM anti-HAV) was not detected in any subjects, and the prevalence rates of IgG anti-HAV were similar in the patients and controls (72.3% and 74.3% in groups 1 and 2, respectively, and 75.7% combined groups 3 and 4). The study indicated a significantly higher risk of acute HEV infection among patients on chronic haemodialysis. It is possible that these were nosocomial infections acquired by person-to-person transmission in the haemodialysis unit. However, it is more probable that the infections were community acquired, a conclusion supported albeit indirectly by the lack of a significant difference between the prevalence in haemodialysis patients (4.8%) and outpatients (1.6%). In areas of endemic HEV, appropriate strategies should be adopted to prevent the risk of HEV among haemodialysis patients.     

Age‐specific seroprevalence of dengue infection in Hong Kong

A newly developed dengue virus vaccine (chimeric yellow fever virus‐tetravalent dengue vaccine [CYD‐TDV]) has recently been licensed for clinical use. The World Health Organization recommends vaccination for populations with seroprevalence of at least 70% to maximize public health impact. This study aimed to delineate the seroprevalence of dengue infection in Hong Kong. A total of 105 972 serum samples submitted for clinical testing during the period 2013‐2015 were age‐stratified and sex‐stratified. For each year of collection, 25 samples were randomly selected from each age‐sex group. Altogether, 2100 samples were tested for the dengue immunoglobulin G (IgG) antibody using a non‐type–specific ELISA kit. The overall dengue IgG‐positive rate was 4.6% and showed no significant change over the 3 years. The positive rate was not associated with sex, but a steep rise in seroprevalence for persons above 65 years (32.7%) was observed. The low dengue seroprevalence in Hong Kong does not support implementation of a national immunization program. Majority of the population in Hong Kong are susceptible to dengue infection, and a substantial proportion of persons older than 65 years could acquire secondary infection and are prone to develop severe dengue.     

Autoimmune pathogenesis in dengue virus infection

The pathogenic mechanisms of dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS) caused by dengue virus (DV) infection remain unresolved. Patients with DHF/DSS are characterized by several manifestations, including severe thrombocytopenia, vascular leakage, and hepatomegaly. In addition to the effect of virus load and virus variation, abnormal immune responses of the host after DV infection may also account for the progression of DHF/DSS. Actually, viral autoimmunity is involved in the pathogenesis of numerous viral infections, such as human immunodeficiency virus, human hepatitis C virus, human cytomegalovirus, herpes simplex virus, Epstein- Barr virus, and DV. In this review, we discuss the implications of autoimmunity in dengue pathogenesis. Antibodies directed against DV nonstructural protein 1 (NS1) showed cross-reactivity with human platelets and endothelial cells, which lead to platelet and endothelial cell damage and inflammatory activation. Based on these findings, we hypothesize that anti-DV NS1 is involved in the pathogenesis of DF and DHF/DSS, and this may provide important information in dengue vaccine development.     

Molecular bases of beta-thalassemia in the Eastern Province of Saudi Arabia

beta-thalassemia is a group of heterogeneous recessive disorders common in many parts of the world. Al-Qatif and Al-Hassa oases in the Eastern Province of Saudi Arabia are regions known for high frequency of these disorders. Using two molecular methods, based on multiplexing-amplification refractory system and reverse hybridization principles, the spectrum of beta-thalassemia in the region was studied. Sixty-nine subjects with known beta-thalassemia disease and volunteers with high hemoglobin $A(2)(HbA(2))$ and low mean corpuscular volume (MCV) were included in this study. Ten mutations were detected in 91% of the subjects under study. Six of these mutations had previously been observed while the other four mutations are reported here for the first time. In addition, four of the mutations accounted for 76.8% of the subjects studied. IVSII-1 (G > A), IVSI-5 (G > A), and codon 39 (C > T) mutations were found to be the most frequent. However, the frequencies of different mutations reported here are slightly different from those reported earlier. A number of these mutations were also found in the neighboring countries, which can be explained in terms of gene flow.     

Molecular epidemiology of human astrovirus infections in Saudi Arabia pediatric patients

Earlier work Tayeb et al. [Tayeb et al. (2008): J Med Virol 80: 1919-1929] set out to study the epidemiology of diarrhea viruses in pediatric populations. The study addressed initially rotavirus, enteric adenovirus, and astrovirus but was later expanded to include norovirus (NoV). Viruses were sought in fecal specimens and characterized for genotype using molecular methods (PCR, RT-PCR, and RFLP) for the first time in KSA. The survey focused on three locations; Jeddah, Makkah, and Riyadh. During the Hajj, the chief population fluxes are via Jeddah to Makkah. One thousand samples were obtained from children (aged 6 years or less) presenting with diarrhea and thus representing community acquired rather than nosocomial infections. Rotavirus was identified in 6% of the samples followed by NoV accounted for 3.5%, astrovirus 1.9%, and adenovirus 1.4%. Rotavirus G9 was characterized for the first time in Saudi Arabia. Adenoviruses were confirmed and further typed using hexon-specific PCR and RFLP. These data were published by Tayeb et al. [Tayeb et al. (2008): J Med Virol 80: 1919-1929]. However, the nature of astrovirus identified was not investigated further. Therefore, more analysis details are appropriate for astrovirus in the Kingdom. As an extension of earlier work carried out on astrovirus serotype distribution in the Kingdom [Tayeb et al. (2008): J Med Virol 80: 1919-1929], a major objective of the project is to use molecular methods to determine the distribution of astrovirus genotype. Such data will help to provide valuable insights into genetic identities and possible sources of virus strains involved not only in pediatric gastroenteritis but also possible outbreaks in the community.     

Pathogenesis of vascular leak in dengue virus infection

Endothelial dysfunction leading to vascular leak is the hallmark of severe dengue. Vascular leak typically becomes clinically evident 3–6 days after the onset of illness, which is known as the critical phase. This critical phase follows the period of peak viraemia, and lasts for 24–48 hr and usually shows rapid and complete reversal, suggesting that it is likely to occur as a result of inflammatory mediators, rather than infection of the endothelium. Cytokines such as tumour necrosis factor‐α, which are known to be elevated in the critical phase of dengue, are likely to be contributing factors. Dengue NS1, a soluble viral protein, has also been shown to disrupt the endothelial glycocalyx and thus contribute to vascular leak, although there appears to be a discordance between the timing of NS1 antigenaemia and occurrence of vascular leak. In addition, many inflammatory lipid mediators are elevated in acute dengue viral infection such as platelet activating factor (PAF) and leukotrienes. Furthermore, many other inflammatory mediators such as vascular endothelial growth factor and angiopoietin‐2 have been shown to be elevated in patients with dengue haemorrhagic fever, exerting their action in part by inducing the activity of phospholipases, which have diverse inflammatory effects including generation of PAF. Platelets have also been shown to significantly contribute to endothelial dysfunction by production of interleukin‐1β through activation of the NLRP3 inflammasome and also by inducing production of inflammatory cytokines by monocytes. Drugs that block down‐stream immunological mediator pathways such as PAF may also be beneficial in the treatment of severe disease.     

Role of antibodies in controlling dengue virus infection

The incidence and disease burden of arthropod-borne flavivirus infections have dramatically increased during the last decades due to major societal and economic changes, including massive urbanization, lack of vector control, travel, and international trade. Specifically, in the case of dengue virus (DENV), the geographical spread of all four serotypes throughout the subtropical regions of the world has led to larger and more severe outbreaks. Many studies have established that recovery from infection by one DENV serotype provides immunity against that serotype, whereas reinfection with another serotype may result in severe disease. Pre-existing antibodies thus play a critical role in controlling viral infection. Both neutralization and enhancement of DENV infection by antibodies are thought to be related to the natural route of viral entry into cells. In this review, we will describe the current knowlegde on the mechanisms involved in flavivirus cell entry and discuss how antibodies may influence the course of infection towards neutralization or enhancement of viral disease.     

Cold urticaria in Saudi Arabia

During an 8-year period we have seen two cases of cold-induced urticaria at the King Faisal Specialist Hospital and Research Centre, a major tertiary centre in Saudi Arabia. This indicates a lower prevalence in Saudi Arabia compared with other countries. One of our patients did not respond to cyproheptadine but she had an excellent response to ketotifen.