MTNR1B genetic polymorphisms as risk factors for gestational diabetes mellitus: a case-control study in a single tertiary care center.

BACKGROUND: Gestational diabetes mellitus (GDM) is a metabolic disease in pregnancy that causes carbohydrate intolerance and hyper-glycemia. Genome-wide association studies and meta-analyses have found that the single nucleotide polymorphisms (SNPs) rs1387153 and rs10830963 of the melatonin receptor 1B ( MTNR1B) gene are associated with GDM. No studies on the MTNR1B gene effect on GDM have been performed in Saudis, other Arabs, or other Middle Eastern populations. OBJECTIVES: Investigate the association of genotype or allele frequencies of the two SNPs with GDM and with clinical parameters related to GDM. DESIGN: Case-control study. SETTINGS: Tertiary care center, Riyadh. PATIENTS AND METHODS: We recruited 400 pregnant Saudi women ages 18-45 years (200 were diagnosed with GDM, and 200 were healthy controls). Biochemical assays were performed, and rs1387153 and rs10830963 polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism analysis and real-time polymerase chain reaction with TaqMan genotyping. MAIN OUTCOME MEASURES: The association of MTNR1B gene (rs1387153 and rs10830963 polymorphisms) with GDM and with biochemical parameters related to GDM. SAMPLE SIZE: 200 GDM cases and 200 non-GDM controls. RESULTS: Differences in allele frequencies for GDM vs non-GMD were statistically significant or nearly significant for both SNPs after adjustment for age and body mass index. In a logistic regression analysis, genotype TT was positively associated with post-prandial blood glucose (P=.018), but other associations were not statistically significant. CONCLUSION: The odds ratios for the associations between the rs1387153 and rs10830963 SNPs and GDM exceeded 1.5-fold, which is higher than typically reported for diseases with complex genetic background. These effect sizes for GDM suggest pregnancy-specific factors related to the MTNR1B risk genotypes. LIMITATIONS: Only two SNPs were studied. CONFLICT OF INTEREST: None.

Assessment of household use of iodized salt and adequacy of salt iodization: a cross-sectional National Study in Saudi Arabia.

OBJECTIVES: This study was conducted to assess household coverage with iodized salt in Saudi Arabia, and to determine adequacy of salt iodization. METHODS: A school-based cross-sectional study using WHO 30-cluster survey methodology. RESULTS: Analysis of 4242 salt samples using qualitative rapid test kit (RTK) revealed that 68.7% (95% CI 67.3-70.1%) were iodized with significant regional differences (p < 0.001). The highest iodized salt samples came from Makkah (82.3%), Riyadh (81.1%) and Maddinah (76.2%) regions, while the least iodized salt samples came from Hail (31.3%), Baha (53.0%), and Northern Borders (57.5%) regions. The national weighted proportion of households consuming iodizes salt was 69.8% (95% CI 69.4-71.2), which is below the Universal Salt Iodization (USI) goal (≥90% coverage). For validation, a quantitative iodometric titration method was used to analyze 775 representative salt samples screened iodized by RTK; iodine content of ≥15 ppm was found in 95.2% (95% CI 93.9-96.5) of samples with median iodine content 51 ppm (mean 50.4 ± 21.8). More than 70% of the iodized salt samples contained iodine concentration higher than the recommended national level (15-40 ppm). CONCLUSIONS: The study revealed inadequate consumption of iodized salt among Saudi households and explored marked regional heterogeneity. The majority of iodized salt samples contained iodine concentration more than the recommended level. These findings imply the need to launch a public awareness campaign on use of iodized salt. Legislation to ban production and sale of non-iodized salt sale for human consumption might be considered. A well-functioning monitoring system at factory level and surveillance system are crucially needed to ensure proper salt iodization and intake.

Undiagnosed Active Pulmonary Tuberculosis among Pilgrims during the 2015 Hajj Mass Gathering: A Prospective Cross-sectional Study.

Mass gatherings pose a risk for tuberculosis (TB) transmission and reactivation of latent TB infection. The annual Hajj pilgrimage attracts 2 million pilgrims many from high TB-endemic countries. We evaluated the burden of undiagnosed active pulmonary TB in pilgrims attending the 2015 Hajj mass gathering. We conducted a prospective cross-sectional study in Mecca, Kingdom of Saudi Arabia, for nonhospitalized adult pilgrims from five high TB-endemic countries. Enrollment criteria were the presence of a cough and the ability to produce a sputum sample. Sputum samples were processed using the Xpert MTB-RIF assay. Data were analyzed for drug-resistant TB, risk factors, and comorbidities by the country of origin. Of 1,164 consenting pilgrims enrolled from five countries: Afghanistan (316), Bangladesh (222), Nigeria (176), Pakistan (302), and South Africa (148), laboratory results were available for 1,063 (91.3%). The mean age of pilgrims was 54.5 (range = 18-94 years) with a male to female ratio of 2.6:1; 27.7% had an underlying comorbidity, with hypertension and diabetes being the most common, 20% were smokers, and 2.8% gave a history of previous TB treatment. Fifteen pilgrims (1.4%) had active previously undiagnosed drug-sensitive pulmonary TB (Afghanistan [12; 80%], Pakistan [2; 13.3%], and Nigeria [1; 6.7%]). No multidrug-resistant TB cases were detected. Pilgrims from high TB-endemic Asian and African countries with undiagnosed active pulmonary TB pose a risk to other pilgrims from over 180 countries. Further studies are required to define the scale of the TB problem during the Hajj mass gathering and the development of proactive screening, treatment and prevention guidelines.

Seroprevalence of Herpes Simplex Virus Type 1 and Type 2 and Coinfection With HIV and Syphilis: The First National Seroprevalence Survey in Saudi Arabia.

BACKGROUND: Herpes simplex virus (HSV) infection is one of the most common viral infections worldwide. Genital herpes is associated with other sexually transmitted infections (STIs) including HIV. Data on prevalence of HSV infections and other STIs in the Kingdom of Saudi Arabia are limited. METHODS: We conducted the first national seroprevalence survey to determine the prevalence and epidemiology of HSV infection among adult Saudis and coinfection with other STIs. Serology was used to detect HSV-1, HSV-2, HIV, and syphilis infections among 4985 participants recruited from across the Kingdom. RESULTS: The overall prevalence of HSV-1 and HSV-2 in the enrolled population was 88.8% and 1.26%, respectively. Although not significant for HSV-2, HSV infection was more prevalent among females, those working, and those who were married (married, divorced, or widowed), especially those married at a younger age. Prevalence of both viruses was statistically significantly higher among those with low education and increased with age. Prevalence of Treponema pallidum antibodies and HIV in the sampled population was very low (0.55% and 0.06%, respectively), as was their prevalence among HSV-2-positive participants (1.6% for both). The correlation between HSV-2 infection and other STIs was significant for HIV (P < 0.0001) but not for T. pallidum antibodies (P = 0.25). CONCLUSIONS: Herpes simplex virus type 1 infection is highly prevalent in Saudi Arabia and mostly acquired before adulthood. Herpes simplex virus type 2 prevalence is very low, acquired in adulthood, and increased with age. Monitoring the prevalence of HSV infection can help inform targeted strategies to prevent new infections, neonatal transmission, and the spread of other STIs in the Kingdom.

Presence of Middle East respiratory syndrome coronavirus antibodies in Saudi Arabia: a nationwide, cross-sectional, serological study.

BACKGROUND: Scientific evidence suggests that dromedary camels are the intermediary host for the Middle East respiratory syndrome coronavirus (MERS-CoV). However, the actual number of infections in people who have had contact with camels is unknown and most index patients cannot recall any such contact. We aimed to do a nationwide serosurvey in Saudi Arabia to establish the prevalence of MERS-CoV antibodies, both in the general population and in populations of individuals who have maximum exposure to camels. METHODS: In the cross-sectional serosurvey, we tested human serum samples obtained from healthy individuals older than 15 years who attended primary health-care centres or participated in a national burden-of-disease study in all 13 provinces of Saudi Arabia. Additionally, we tested serum samples from shepherds and abattoir workers with occupational exposure to camels. Samples were screened by recombinant ELISA and MERS-CoV seropositivity was confirmed by recombinant immunofluorescence and plaque reduction neutralisation tests. We used two-tailed Mann Whitney U exact tests, χ(2), and Fisher's exact tests to analyse the data. FINDINGS: Between Dec 1, 2012, and Dec 1, 2013, we obtained individual serum samples from 10,009 individuals. Anti-MERS-CoV antibodies were confirmed in 15 (0·15%; 95% CI 0·09-0·24) of 10,009 people in six of the 13 provinces. The mean age of seropositive individuals was significantly younger than that of patients with reported, laboratory-confirmed, primary Middle Eastern respiratory syndrome (43·5 years [SD 17·3] vs 53·8 years [17·5]; p=0·008). Men had a higher antibody prevalence than did women (11 [0·25%] of 4341 vs two [0·05%] of 4378; p=0·028) and antibody prevalence was significantly higher in central versus coastal provinces (14 [0·26%] of 5479 vs one [0·02%] of 4529; p=0·003). Compared with the general population, seroprevalence of MERS-CoV antibodies was significantly increased by 15 times in shepherds (two [2·3%] of 87, p=0·0004) and by 23 times in slaughterhouse workers (five [3·6%] of 140; p<0·0001). INTERPRETATION: Seroprevalence of MERS-CoV antibodies was significantly higher in camel-exposed individuals than in the general population. By simple multiplication, a projected 44,951 (95% CI 26,971-71,922) individuals older than 15 years might be seropositive for MERS-CoV in Saudi Arabia. These individuals might be the source of infection for patients with confirmed MERS who had no previous exposure to camels. FUNDING: European Union, German Centre for Infection Research, Federal Ministry of Education and Research, German Research Council, and Ministry of Health of Saudi Arabia.

Environmental sampling for respiratory pathogens in Jeddah airport during the 2013 Hajj season.

BACKGROUND: Respiratory tract infections (RTIs) are common during the Hajj season and are caused by a variety of organisms, which can be transmitted via the air or contaminated surfaces. We conducted a study aimed at sampling the environment in the King Abdul Aziz International (KAAI) Airport, Pilgrims City, Jeddah, during Hajj season to detect respiratory pathogens. METHODS: Active air sampling was conducted using air biosamplers, and swabs were used to sample frequently touched surfaces. A respiratory multiplex array was used to detect bacterial and viral respiratory pathogens. RESULTS: Of the 58 environmental samples, 8 were positive for at least 1 pathogen. One air sample (1 of 18 samples, 5.5%) tested positive for influenza B virus. Of the 40 surface samples, 7 (17.5%) were positive for pathogens. These were human adenovirus (3 out of 7, 42.8%), human coronavirus OC43/HKU1 (3 out of 7, 42.8%), Haemophilus influenzae (1 out of 7, 14.2%), and Moraxella catarrhalis (1 out of 7, 14.2%). Chair handles were the most commonly contaminated surfaces. The handles of 1 chair were cocontaminated with coronavirus OC43/HKU1 and H influenzae. CONCLUSION: Respiratory pathogens were detected in the air and on surfaces in the KAAI Airport in Pilgrims City. Larger-scale studies based on our study are warranted to determine the role of the environment in transmission of respiratory pathogens during mass gathering events (eg, Hajj) such that public health preventative measures might be better targeted.

Etiology of severe community-acquired pneumonia during the 2013 Hajj-part of the MERS-CoV surveillance program.

BACKGROUND: Pneumonia is the leading cause of hospital admission during the annual Islamic pilgrimage (Hajj). The etiology of severe pneumonia is complex and includes the newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV). Since 2012, the Saudi Ministry of Health (MoH) has required screening for MERS-CoV for all cases of severe pneumonia requiring hospitalization. We aimed to screen Hajj pilgrims admitted to healthcare facilities in 2013 with severe community-acquired pneumonia (CAP) for MERS-CoV and to determine other etiologies. METHODS: Sputum samples were collected from all pilgrims admitted to 15 healthcare facilities in the cities of Makkah and Medina, Saudi Arabia, who were diagnosed with severe CAP on admission, presenting with bilateral pneumonia. The medical records were reviewed to collect information on age, gender, nationality, and patient outcome. Samples were screened for MERS-CoV by PCR, and a respiratory multiplex array was used to detect up to 22 other viral and bacterial respiratory pathogens. RESULTS: Thirty-eight patients met the inclusion criteria; they were predominantly elderly (mean age 58.6 years, range 25-83 years) and male (68.4%), and all were from developing countries. Fourteen of the 38 patients died (36.8%). MERS-CoV was not detected in any of the samples. Other respiratory pathogens were detected in 26 (68.4%) samples. Of these, bacterial pathogens were detected in 84.6% (22/26) and viruses in 80.7% (21/26). Twenty-one (80.7%) samples were positive for more than one respiratory pathogen and 17 (65.3%) were positive for both bacteria and viruses. The most common respiratory virus was human rhinovirus, detected in 57.7% of the positive samples, followed by influenza A virus (23.1%) and human coronaviruses (19.2%). Haemophilus influenzae and Streptococcus pneumoniae were the predominant bacteria, detected in 57.7% and 53.8%, respectively, of the positive samples, followed by Moraxella catarrhalis (36.4%). CONCLUSIONS: MERS-CoV was not the cause of severe CAP in any of the hospitalized pilgrims investigated. However we identified a variety of other respiratory pathogens in the sputum of this small number of patients. This indicates that the etiology of severe CAP in Hajj is complex with implications regarding its management.

Prevalence of MERS-CoV nasal carriage and compliance with the Saudi health recommendations among pilgrims attending the 2013 Hajj.

BACKGROUND: Annually, Saudi Arabia is the host of the Hajj mass gathering. We aimed to determine the Middle East respiratory syndrome coronavirus (MERS-CoV) nasal carriage rate among pilgrims performing the 2013 Hajj and to describe the compliance with the Saudi Ministry of Health vaccine recommendations. METHOD: Nasopharyngeal samples were collected from 5235 adult pilgrims from 22 countries and screened for MERS-CoV using reverse transcriptase-polymerase chain reaction. Information regarding the participants' age, gender, country of origin, medical conditions, and vaccination history were obtained. RESULTS: The mean age of the screened population was 51.8 years (range, 18-93 years) with a male/female ratio of 1.17:1. MERS-CoV was not detected in any of the samples tested (3210 pre-Hajj and 2025 post-Hajj screening). According to the vaccination documents, all participants had received meningococcal vaccination and the majority of those from at-risk countries were vaccinated against yellow fever and polio. Only 22% of the pilgrims (17.5% of those ≥65 years and 36.3% of diabetics) had flu vaccination, and 4.4% had pneumococcal vaccination. CONCLUSION: There was no evidence of MERS-CoV nasal carriage among Hajj pilgrims. While rates of compulsory vaccinations uptake were high, uptake of pneumococcal and flu seasonal vaccinations were low, including among the high-risk population.

Structural relationships and cellular tropism of staphylococcal superantigen-like proteins.

The staphylococcal superantigen-like proteins (SSLs) are a family of polymorphic paralogs encoded in the Staphylococcus aureus genome whose function is unknown. The crystal structure of SSL7 was determined and compared to that of SSL5 and that of a classical superantigen, streptococcal pyrogenic exotoxin. Although the overall architecture of the superantigen family is retained in both SSL7 and SSL5, there are significant differences in the structures which suggest that the characteristic major histocompatibility complex binding site of superantigens has been lost. To complement these data, the abilities of SSL7 and a closely related paralog, SSL9, to interact with cells of the immune system were investigated. In populations of human white blood cells, both SSLs interacted selectively with monocytes via specific saturable but separate binding sites, which led to rapid uptake of the SSLs. In addition, SSLs were rapidly taken up by dendritic cells, but not by macrophages, into the same endosomal compartment as dextran. The ability of these secreted proteins to target antigen-presenting cells may enhance a misplaced antibody response against the proteins, which may facilitate bacterial colonization rather than contribute to host protection. Like classical superantigens, therefore, SSLs may distract the host's immune system, but they may do so via entirely different molecular mechanisms.