The landscape of genetic diseases in Saudi Arabia based on the first 1000 diagnostic panels and exomes.

In this study, we report the experience of the only reference clinical next-generation sequencing lab in Saudi Arabia with the first 1000 families who span a wide-range of suspected Mendelian phenotypes. A total of 1019 tests were performed in the period of March 2016-December 2016 comprising 972 solo (index only), 14 duo (parents or affected siblings only), and 33 trio (index and parents). Multigene panels accounted for 672 tests, while whole exome sequencing (WES) represented the remaining 347 tests. Pathogenic or likely pathogenic variants that explain the clinical indications were identified in 34% (27% in panels and 43% in exomes), spanning 279 genes and including 165 novel variants. While recessive mutations dominated the landscape of solved cases (71% of mutations, and 97% of which are homozygous), a substantial minority (27%) were solved on the basis of dominant mutations. The highly consanguineous nature of the study population also facilitated homozygosity for many private mutations (only 32.5% of the recessive mutations are founder), as well as the first instances of recessive inheritance of previously assumed strictly dominant disorders (involving ITPR1, VAMP1, MCTP2, and TBP). Surprisingly, however, dual molecular diagnosis was only observed in 1.5% of cases. Finally, we have encountered candidate variants in 75 genes (ABHD6, ACY3, ADGRB2, ADGRG7, AGTPBP1, AHNAK2, AKAP6, ASB3, ATXN1L, C17orf62, CABP1, CCDC186, CCP110, CLSTN2, CNTN3, CNTN5, CTNNA2, CWC22, DMAP1, DMKN, DMXL1, DSCAM, DVL2, ECI1, EP400, EPB41L5, FBXL22, GAP43, GEMIN7, GIT1, GRIK4, GRSF1, GTRP1, HID1, IFNL1, KCNC4, LRRC52, MAP7D3, MCTP2, MED26, MPP7, MRPS35, MTDH, MTMR9, NECAP2, NPAT, NRAP, PAX7, PCNX, PLCH2, PLEKHF1, PTPN12, QKI, RILPL2, RIMKLA, RIMS2, RNF213, ROBO1, SEC16A, SIAH1, SIRT2, SLAIN2, SLC22A20, SMDT1, SRRT, SSTR1, ST20, SYT9, TSPAN6, UBR4, VAMP4, VPS36, WDR59, WDYHV1, and WHSC1) not previously linked to human phenotypes and these are presented to accelerate post-publication matchmaking. Two of these genes were independently mutated in more than one family with similar phenotypes, which substantiates their link to human disease (AKAP6 in intellectual disability and UBR4 in early dementia). If the novel candidate disease genes in this cohort are independently confirmed, the yield of WES will have increased to 83%, which suggests that most "negative" clinical exome tests are unsolved due to interpretation rather than technical limitations.

13-valent pneumococcal conjugate vaccine (PCV13) is immunogenic and safe in children 6-17 years of age with sickle cell disease previously vaccinated with 23-valent pneumococcal polysaccharide vaccine (PPSV23): Results of a phase 3 study.

BACKGROUND: A large population of older children with sickle cell disease (SCD) is currently vaccinated with only 23-valent pneumococcal polysaccharide vaccine (PPSV23). In immunocompetent adults, PPSV23 vaccination reduces immune responses to subsequent vaccination with a pneumococcal vaccine. The 13-valent pneumococcal conjugate vaccine (PCV13), which addresses this limitation, may offer an advantage to this population at high risk of pneumococcal disease. PROCEDURE: Children with SCD 6-17 years of age previously vaccinated with PPSV23 at least 6 months before study enrollment received two doses of PCV13 6 months apart. Anti-pneumococcal polysaccharide immunoglobulin G (IgG) geometric mean concentrations (GMCs) and opsonophagocytic activity (OPA) geometric mean titers (GMTs) were measured before, 1 month after each administration, and 1 year after the second administration. RESULTS: Following each PCV13 administration, IgG GMCs and OPA GMTs significantly increased, and antibody levels after doses 1 and 2 were generally comparable. Antibody levels declined over the year following dose 2. At 1 year after the second administration, OPA GMTs for all and IgG GMCs for most serotypes remained above pre-vaccination levels. Most adverse events were due to vaso-occlusive crises, a characteristic of the underlying condition of SCD. CONCLUSIONS: Children with SCD who were previously vaccinated with PPSV23 responded well to 1 PCV13 dose, and a second dose did not increase antibody response. PCV13 antibodies persisted above pre-vaccination levels for all serotypes 1 year after dose 2. Children with SCD may benefit from at least one dose of PCV13.

Transmission and evolution of the Middle East respiratory syndrome coronavirus in Saudi Arabia: a descriptive genomic study.

BACKGROUND: Since June, 2012, Middle East respiratory syndrome coronavirus (MERS-CoV) has, worldwide, caused 104 infections in people including 49 deaths, with 82 cases and 41 deaths reported from Saudi Arabia. In addition to confirming diagnosis, we generated the MERS-CoV genomic sequences obtained directly from patient samples to provide important information on MERS-CoV transmission, evolution, and origin. METHODS: Full genome deep sequencing was done on nucleic acid extracted directly from PCR-confirmed clinical samples. Viral genomes were obtained from 21 MERS cases of which 13 had 100%, four 85-95%, and four 30-50% genome coverage. Phylogenetic analysis of the 21 sequences, combined with nine published MERS-CoV genomes, was done. FINDINGS: Three distinct MERS-CoV genotypes were identified in Riyadh. Phylogeographic analyses suggest the MERS-CoV zoonotic reservoir is geographically disperse. Selection analysis of the MERS-CoV genomes reveals the expected accumulation of genetic diversity including changes in the S protein. The genetic diversity in the Al-Hasa cluster suggests that the hospital outbreak might have had more than one virus introduction. INTERPRETATION: We present the largest number of MERS-CoV genomes (21) described so far. MERS-CoV full genome sequences provide greater detail in tracking transmission. Multiple introductions of MERS-CoV are identified and suggest lower R0 values. Transmission within Saudi Arabia is consistent with either movement of an animal reservoir, animal products, or movement of infected people. Further definition of the exposures responsible for the sporadic introductions of MERS-CoV into human populations is urgently needed. FUNDING: Saudi Arabian Ministry of Health, Wellcome Trust, European Community, and National Institute of Health Research University College London Hospitals Biomedical Research Centre.

Gains of glycosylation comprise an unexpectedly large group of pathogenic mutations.

Mutations involving gains of glycosylation have been considered rare, and the pathogenic role of the new carbohydrate chains has never been formally established. We identified three children with mendelian susceptibility to mycobacterial disease who were homozygous with respect to a missense mutation in IFNGR2 creating a new N-glycosylation site in the IFNgammaR2 chain. The resulting additional carbohydrate moiety was both necessary and sufficient to abolish the cellular response to IFNgamma. We then searched the Human Gene Mutation Database for potential gain-of-N-glycosylation missense mutations; of 10,047 mutations in 577 genes encoding proteins trafficked through the secretory pathway, we identified 142 candidate mutations ( approximately 1.4%) in 77 genes ( approximately 13.3%). Six mutant proteins bore new N-linked carbohydrate moieties. Thus, an unexpectedly high proportion of mutations that cause human genetic disease might lead to the creation of new N-glycosylation sites. Their pathogenic effects may be a direct consequence of the addition of N-linked carbohydrate.

Omicron variants of SARS-CoV-2: Epidemiological and clinical insights from a tertiary care center in Saudi Arabia.

BACKGROUND: The actual burden of the Omicron variants remains unclear. Therefore, this study aims to analyze the epidemiological and clinical features of Omicron-infected patients and investigate factors influencing hospital admission. METHODS: This retrospective single-center study included individuals with positive SARS-CoV-2 infection, specifically the Omicron variants (XBB, EG or JN), identified through real-time reverse-transcriptase polymerase chain reaction assays from January 2022 to December 2023. RESULTS: A total of 305 Omicron-infected patients were included; (53.11 %) were females and (46.89 %) were males, with a median age of 39 years [interquartile range (IQR): 30, 53]. Underlying diseases, including endocrine/metabolic disorders (22.30 %), hypertension (12.79 %), chronic respiratory disease (10.49 %), and malignancy (9.18 %) were prevalent, while (40.98 %) were medically free. The XBB variant was predominant (73.11 %), followed by JN (20.33 %), and EG variant (6.56 %). The seasonality analysis demonstrates XBB variants' domination in 2022, with a surge to 40 cases in December. The trend continued in 2023, peaking at 76 XBB cases in March. May 2023 reported 38 XBB cases and the emergence of 17 EG instances. Notably, in December, only one XBB case was reported, and 62 instances emerged with the JN variant. Overall, 233 out of 305 cases were reported during flu season (September to March) (76.39 %). Moreover, hospitalization occurred in (16.39 %), with a (1.31 %) mortality rate (all deaths in the JN variant). Multivariable analysis confirmed renal disease, chronic respiratory disease, endocrine/metabolism issues, and polymicrobial infection as positive predictors of hospitalization (p < 0.05). While COVID-19 vaccination significantly reduced hospitalization odds (Odds Ratio: 0.20, p = 0.001). CONCLUSIONS: These findings contribute valuable insights into Omicron epidemiology and factors influencing hospitalization. The dynamic fluctuations in Omicron variants, particularly XBB, EG, and JN, over 2022 and 2023, with JN emerging as the dominant circulating variant globally, underscore the need for continuous vigilance and urgency for updated vaccine formulations.

Evolving Epidemiology of Pediatric Respiratory Syncytial Virus (RSV) Cases Around COVID-19 Pandemic: Impact and Clinical Insights, Retrospective Cohort Study.

BACKGROUND: The burden of respiratory syncytial virus (RSV) in high-risk pediatric patients remains unclear. Therefore, this study aims to characterize pediatric RSV cases from January 2019 to December 2022 and assess the impact of the COVID-19 pandemic on RSV burden and RSV-related outcomes. In addition, examining factors influencing RSV-related hospitalization. METHODS: This is a retrospective study that included pediatric patients (aged 14 and below) who presented at King Faisal Specialist Hospital and Research Centre (KFSHRC) in Riyadh, Saudi Arabia with RSV infection identified using real-time reverse-transcriptase polymerase chain reaction assays. Statistical analyses were performed using STATA. RESULTS: A total of 885 RSV cases were reported; (56.05%) were males and (43.95%) were females with a median age of 24 months [interquartile range (IQR): 11-60]. 534 (60.34%) required hospitalization. As for RSV seasonality, there was a significant increase in RSV prevalence following the COVID-19 pandemic, escalating from 205 cases in 2019 to 425 cases in 2022. The increase in 2022 was evident in January and persisted from September to December, reaching its peak during the months of October (20.70% - 88 cases) and November (32.00% - 136 cases). About (27.12%) of RSV infected children were medically free patients. Symptomatic patients exhibited various clinical manifestations, with ventilation necessary in (13.11%) of cases. Further analysis revealed significant changes in RSV-related outcomes post-COVID-19, including a decrease in hospitalization rates, an increase in medically free patients, and a lower need for ventilation (p < 0.05). Notably, a significant proportion of RSV admissions occurred within the first 6 months of life, with (77.69%) in the age group of 0 to 5 months. In addition, previous RSV infection, prematurity, low birth weight, renal disease, congenital heart disease, endocrine/metabolic disease, neuro/neuromuscular diseases, and genetic disorders were positively associated with hospitalization (P < 0.05). Interestingly, asthma and bone marrow transplantation were negatively associated with hospitalization (P < 0.05). The mortality rate in this study is (2.37%) (21/885). CONCLUSION: This study provides a comprehensive understanding of the demographic and clinical factors influencing RSV outcomes, highlighting the impact of the COVID-19 pandemic and shedding light on potential risk factors for RSV-related hospitalization. The highest prevalence of RSV during (September to January), aligning with global patterns and emphasizing the importance of timing in preventive strategies.

Epidemiology, clinical profiles, and antimicrobial susceptibility of Elizabethkingia meningoseptica infections: Insights from a tertiary care hospital in Saudi Arabia.

OBJECTIVES: To investigate the incidence rate, clinical characteristics across different age groups, antimicrobial susceptibility, and outcomes of Elizabethkingia meningoseptica (E. meningoseptica) infections. METHODS: A retrospective analysis was carried out to include 66 cases with confirmed E. meningoseptica cultures from sterile samples between January 2014 and June 2022 at King Faisal Specialist Hospital and Research Centre in Riyadh, Saudi Arabia. RESULTS: A total of 66 cases were identified, with an incidence rate of 0.3 per 1000 admissions. Most cases were hospital-acquired (80.3%), primarily in critical care areas. All patients had underlying diseases, with respiratory (40.9%) and cardiovascular (39.4%) diseases being the most common. Minocycline showed the highest susceptibility (96.0%), followed by trimethoprim/sulfamethoxazole (77.0%), whereas tobramycin and colistin were fully resistant. The in-hospital mortality rate was 34.8%, whereas the 28-day mortality rate was 22.7%. Clinical characteristics across age groups showed a higher prevalence of cardiovascular disease in pediatrics than in adults, whereas exposure to mechanical ventilation, immunosuppressive therapy, previous infection, anemia, and in-hospital mortality were reported more frequently in adults (p<0.05). CONCLUSION: Our study provides valuable insights into E. meningoseptica infection in Saudi Arabia, emphasizing the importance of robust infection control measures. Incidence and mortality rates align with global trends. Variations in clinical characteristics across age groups highlight the importance of tailored treatments based on patient demographics and underlying comorbidities.

Selective predisposition to bacterial infections in IRAK-4-deficient children: IRAK-4-dependent TLRs are otherwise redundant in protective immunity.

Human interleukin (IL) 1 receptor-associated kinase 4 (IRAK-4) deficiency is a recently discovered primary immunodeficiency that impairs Toll/IL-1R immunity, except for the Toll-like receptor (TLR) 3- and TLR4-interferon (IFN)-alpha/beta pathways. The clinical and immunological phenotype remains largely unknown. We diagnosed up to 28 patients with IRAK-4 deficiency, tested blood TLR responses for individual leukocyte subsets, and TLR responses for multiple cytokines. The patients' peripheral blood mononuclear cells (PBMCs) did not induce the 11 non-IFN cytokines tested upon activation with TLR agonists other than the nonspecific TLR3 agonist poly(I:C). The patients' individual cell subsets from both myeloid (granulocytes, monocytes, monocyte-derived dendritic cells [MDDCs], myeloid DCs [MDCs], and plasmacytoid DCs) and lymphoid (B, T, and NK cells) lineages did not respond to the TLR agonists that stimulated control cells, with the exception of residual responses to poly(I:C) and lipopolysaccharide in MDCs and MDDCs. Most patients (22 out of 28; 79%) suffered from invasive pneumococcal disease, which was often recurrent (13 out of 22; 59%). Other infections were rare, with the exception of severe staphylococcal disease (9 out of 28; 32%). Almost half of the patients died (12 out of 28; 43%). No death and no invasive infection occurred in patients older than 8 and 14 yr, respectively. The IRAK-4-dependent TLRs and IL-1Rs are therefore vital for childhood immunity to pyogenic bacteria, particularly Streptococcus pneumoniae. Conversely, IRAK-4-dependent human TLRs appear to play a redundant role in protective immunity to most infections, at most limited to childhood immunity to some pyogenic bacteria.

Impaired response to interferon-alpha/beta and lethal viral disease in human STAT1 deficiency.

The receptors for interferon-alpha/beta (IFN-alpha/beta) and IFN-gamma activate components of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway, leading to the formation of at least two transcription factor complexes. STAT1 interacts with STAT2 and p48/IRF-9 to form the transcription factor IFN-stimulated gene factor 3 (ISGF3). STAT1 dimers form gamma-activated factor (GAF). ISGF3 is induced mainly by IFN-alpha/beta, and GAF by IFN-gamma, although both factors can be activated by both types of IFN. Individuals with mutations in either chain of the IFN-gamma receptor (IFN-gammaR) are susceptible to infection with mycobacteria. A heterozygous STAT1 mutation that impairs GAF but not ISGF3 activation has been found in other individuals with mycobacterial disease. No individuals with deleterious mutations in the IFN-alpha/beta signaling pathway have been described. We report here two unrelated infants homozygous with respect to mutated STAT1 alleles. Neither IFN-alpha/beta nor IFN-gamma activated STAT1-containing transcription factors. Like individuals with IFN-gammaR deficiency, both infants suffered from mycobacterial disease, but unlike individuals with IFN-gammaR deficiency, both died of viral disease. Viral multiplication was not inhibited by recombinant IFN-alpha/beta in cell lines from the two individuals. Inherited impairment of the STAT1-dependent response to human IFN-alpha/beta thus results in susceptibility to viral disease.

A novel form of human STAT1 deficiency impairing early but not late responses to interferons.

Autosomal recessive STAT1 deficiency is associated with impaired cellular responses to interferons and susceptibility to intracellular bacterial and viral infections. We report here a new form of partial STAT1 deficiency in 2 siblings presenting mycobacterial and viral diseases. Both carried a homozygous missense mutation replacing a lysine with an asparagine residue at position 201 (K201N) of STAT1. This mutation causes the abnormal splicing out of exon 8 from most STAT1 mRNAs, thereby decreasing (by ~ 70%) STAT1 protein levels. The mutant STAT1 proteins are not intrinsically deleterious, in terms of tyrosine phosphorylation, dephosphorylation, homodimerization into γ-activating factor and heterotrimerization into ISGF-3, binding to specific DNA elements, and activation of the transcription. Interestingly, the activation of γ-activating factor and ISGF3 was impaired only at early time points in the various cells from patient (within 1 hour of stimulation), whereas sustained impairment occurs in other known forms of complete and partial recessive STAT1 deficiency. Consequently, delayed responses were normal; however, the early induction of interferon-stimulated genes was selectively and severely impaired. Thus, the early cellular responses to human interferons are critically dependent on the amount of STAT1 and are essential for the appropriate control of mycobacterial and viral infections.

Observational cohort study of perinatal outcomes of women with COVID-19.

BACKGROUND: Understanding the impact of SARS-CoV-2 infection on pregnancy outcomes and of pregnancy on COVID-19 outcomes is critical for ensuring proper prenatal and antenatal care. No similar studies have been published in Saudi Arabia. METHODS: We performed a prospective cohort study of pregnant women with confirmed SARS-CoV-2 infection who presented at King Faisal Specialist Hospital and Research Center (KFSHRC) in Riyadh, Kingdom of Saudi Arabia. COVID-19 staging was performed, pregnancy-related complications were assessed, and neonatal infection was evaluated. RESULTS: We enrolled 81 patients (mean age 31.75 years, SD 5.25) of which there were 17 cases in the first trimester, 20 in the second trimester, and 34 in the third trimester. The distribution of COVID-19 severity was 40 patients with Stage A, 36 with Stage B, 4 with Stage C, and 1 with Stage D. Complications were pregnancy loss in 2 patients (one in each first and second trimester) and 1 fetal death after 20 weeks of pregnancy, 7 patients with fetal growth restriction, and 8 with pre-term delivery. CONCLUSIONS: We did not observe an unusual frequency of pregnancy-related complications due to SARS-CoV-2 infection in this high-risk obstetric population and there was no evidence of vertical transmission in newborns from women who delivered while positive for the virus.

Stenotrophomonas maltophilia bacteremia in children: risk factors and mortality rate.

PURPOSE: Stenotrophomonas maltophilia (S. maltophilia) is an opportunistic and nosocomial pathogen that can cause an invasive and fatal infection, particularly in hospitalized and immunocompromised patients. However, little is known about the impact of S. maltophilia bacteremia in pediatric patients. Therefore, we aimed to identify risk factors for mortality, antibiotics susceptibility to S. maltophilia, and mortality rates in pediatric patients with S. maltophilia bacteremia. METHODS: We conducted a retrospective cohort study by identifying all S. maltophilia positive blood cultures in the microbiology laboratory database between January 2007 and December 2018 from hospitalized pediatric patients (age 1-14 years). After identifying patients with S. maltophilia bacteremia, medical charts were reviewed for demographics, clinical data, and outcomes within seven days of bacteremia diagnosis. Risk factors associated with mortality in S. maltophilia bacteremia patients were determined using univariate and multivariate analyses. FINDINGS: Sixty-eight pediatric patients with S. maltophilia bacteremia were identified. All infections were nosocomial infections, and (88.2%) bacteremia cases were catheter-related bloodstream infections. On multivariate analysis, ICU admission prior to bacteremia episode and neutropenia were the major risk factors associated with mortality. S. maltophilia was the most susceptible to trimethoprim and sulfamethoxazole (TMP/SMX, 94.1%), followed by levofloxacin (85.7%). The overall mortality rate within seven days of S. maltophilia bacteremia diagnosis was 33.8%. CONCLUSION: S. maltophilia bacteremia is a devastating emerging infection associated with high mortality among hospitalized children. Therefore, early diagnosis and prompt management based on local susceptibility data are crucial. Various risk factors, especially ICU admission prior to bacteremia episode and neutropenia, are associated with S. maltophilia bacteremia mortality.

Low penetrance, broad resistance, and favorable outcome of interleukin 12 receptor beta1 deficiency: medical and immunological implications.

The clinical phenotype of interleukin 12 receptor beta1 chain (IL-12Rbeta1) deficiency and the function of human IL-12 in host defense remain largely unknown, due to the small number of patients reported. We now report 41 patients with complete IL-12Rbeta1 deficiency from 17 countries. The only opportunistic infections observed, in 34 patients, were of childhood onset and caused by weakly virulent Salmonella or Mycobacteria (Bacille Calmette-Guérin -BCG- and environmental Mycobacteria). Three patients had clinical tuberculosis, one of whom also had salmonellosis. Unlike salmonellosis, mycobacterial infections did not recur. BCG inoculation and BCG disease were both effective against subsequent environmental mycobacteriosis, but not against salmonellosis. Excluding the probands, seven of the 12 affected siblings have remained free of case-definition opportunistic infection. Finally, only five deaths occurred in childhood, and the remaining 36 patients are alive and well. Thus, a diagnosis of IL-12Rbeta1 deficiency should be considered in children with opportunistic mycobacteriosis or salmonellosis; healthy siblings of probands and selected cases of tuberculosis should also be investigated. The overall prognosis is good due to broad resistance to infection and the low penetrance and favorable outcome of infections. Unexpectedly, human IL-12 is redundant in protective immunity against most microorganisms other than Mycobacteria and Salmonella. Moreover, IL-12 is redundant for primary immunity to Mycobacteria and Salmonella in many individuals and for secondary immunity to Mycobacteria but not to Salmonella in most.

A role for interleukin-12/23 in the maturation of human natural killer and CD56+ T cells in vivo.

Natural killer (NK) cells have been originally defined by their "naturally occurring" effector function. However, only a fraction of human NK cells is reactive toward a panel of prototypical tumor cell targets in vitro, both for the production of interferon-gamma (IFN-gamma) and for their cytotoxic response. In patients with IL12RB1 mutations that lead to a complete IL-12Rbeta1 deficiency, the size of this naturally reactive NK cell subset is diminished, in particular for the IFN-gamma production. Similar data were obtained from a patient with a complete deficit in IL-12p40. In addition, the size of the subset of effector memory T cells expressing CD56 was severely decreased in IL-12Rbeta1- and IL-12p40-deficient patients. Human NK cells thus require in vivo priming with IL-12/23 to acquire their full spectrum of functional reactivity, while T cells are dependent upon IL-12/23 signals for the differentiation and/or the maintenance of CD56(+) effector memory T cells. The susceptibility of IL-12/23 axis-deficient patients to Mycobacterium and Salmonella infections in combination with the absence of mycobacteriosis or salmonellosis in the rare cases of human NK cell deficiencies point to a role for CD56(+) T cells in the control of these infections in humans.

The first case of Raoultella planticola infective endocarditis in a 4 year old child: A case report and review of literature.

Infective endocarditis is a complication of bacteremia that can lead to serious morbidity and even mortality if not appropriately treated, well known organisms commonly lead to this condition in many repeated scenarios so they are usually recognized and treated, but if it was caused by other organisms its detection and treatment can be harder. Raoultella planticola, a low virulent organism used to be part of the Klebsiella species, has been found in many reports to cause multiple human conditions. In this article, a novel case of R. planticola is reported, and the organism was reviewed in many aspects for clinician to be able to recognize this infection and manage it in a more effective way.

Approach to recurrent Herpes Simplex Encephalitis in children.

Herpes Simplex Encephalitis (HSE) is one of the commonest viral encephalitis and its recurrence is being increasingly reported were HSE relapse rate came up to 5%. Both herpes simplex virus (HSV) types can lead to encephalitis and it was established that HSV-1 is capable of nervous system invasion, latency, and recurrence. The recurrence of HSE used to be attributed to immunological compromise, but reports show many cases have no obvious immune system impairment. Further investigations revealed genetic predispositions to HSV infection that would explain the host vulnerability to its recurrence. In this review, we discuss the gene mutations that may predispose to recurrent HSE and the importance of early diagnosis and treatment.

Guidelines for the secondary prevention of rheumatic heart disease: Endorsed by Saudi Pediatric Infectious Diseases Society (SPIDS).

Rheumatic fever is a rare yet serious condition develop as a consequence of throat infection caused by Streptococcus pyogenes. It is the leading cause for rheumatic heart disease. Rheumatic heart disease is a worldwide public health concern. It is a chronic condition that results in carditis, irreversible valve damage and heart failure in children and young adults living in low-income countries. The age of onset peaks between 5 and 15 years. Approximately, 3% of patients with untreated acute streptococcal sore throats develop rheumatic fever. Rheumatic fever and rheumatic heart disease can be prevented with appropriate antibiotics administration to prevent the progression of valve damage. The current use of primary and secondary prevention antibiotics in Saudi Arabia is not known. Therefore, this clinical practice guideline is developed, based on the best available evidence, to promote appropriate antibiotics secondary prophylaxis use for prevention of rheumatic heart disease.

Avian influenza: are our feathers ruffled?

During the past century, three major influenza pandemics took place, leading to a devastating number of deaths. Pandemics occur through the emergence of a new strain of influenza virus that can infect humans, to which there is little pre-existing immunity and which spreads easily from human to human. The H5N1 influenza virus has the potential of becoming a pandemic virus, since it can infect humans and is highly pathogenic. All that remains is the final step of acquiring the genetic material to enable efficient human-to-human transmission. Therefore, the World Health Organization (WHO) has declared pandemic alert phase 3, the last phase before there is actual evidence of increased and efficient human-to-human transmission. In addition, every case of transmission of an avian influenza virus to humans is regarded by WHO as a cause for heightened alertness and surveillance. The circulation of highly pathogenic avian influenza viruses in large numbers among the poultry population in a growing number of countries is a major concern. Since the influenza viruses are highly unstable, the co-circulation of highly pathogenic animal viruses with human viruses may create opportunities for different species-specific viruses to exchange genetic material, giving rise to a new influenza virus to which humans would have little, if any, protective immunity. In this article, we highlight the current avian influenza situation from its different aspects with a special focus on the Hajj since we host over 2 million pilgrims a year in the holy cities of Mekkah and Medina.

Human immunodeficiency virus infection in Saudi Arabian children: transmission, clinical manifestations and outcome.

BACKGROUND: Vertical transmission from mother to infant is the most common mode of transmission of HIV infection in children. Data on pediatric HIV in the Middle East and Gulf region are scarce. We describe the spectrum, characteristics and outcome of HIV infection in Saudi children. METHODS: We collected descriptive data on HIV-infected or exposed children seen at the King Faisal Hospital and Research Centre (KFSH&RC) between 1986 and 2003. RESULTS: Sixty-three children had proven HIV infection. The source of infection was perinatal transmission in 63.5% of cases and contaminated blood or blood products transfusion in 34.5%. Median age at diagnosis was 6 years. In 42 patients for whom complete records were available, 90% were delivered by spontaneous vaginal delivery and 10% by cesarean delivery. Ninety-three percent of infected infants were breastfed throughout infancy. The complete medical records were available for 66% of children; for the remainder, part of the records could not be retrieved. Thirteen percent had an AIDS-defining opportunistic infection, with disseminated cytomegalovirus (CMV) infection being the most common (37.5%). All cases received antiretroviral therapy starting in 1997. Of those who received highly active antiretroviral therapy, 79% were compliant with treatment and had a sustained virologic response below the detectable level. Seventy-five percent of those diagnosed before 1995 died compared with 7.7% diagnosed later. CONCLUSION: Effective preventive measures, such as antiretroviral prophylaxis, cesarean delivery, and abstention from breastfeeding are not being applied. This could be largely due to lack of knowledge among patients and healthcare providers. Physicians must recognize the signs and symptoms of HIV infection, and have a high index of suspicion so that infected children are diagnosed early and referred to a specialized center for treatment and follow-up.

Guidelines for palivizumab prophylaxis in infants and young children at increased risk for respiratory syncytial virus infection in Saudi Arabia.

Respiratory syncytial virus (RSV) is a leading cause of serious seasonal lower respiratory tract infections (LRTI) in high-risk infants and children, with epidemics occurring annually in Saudi Arabia from October to March. Premature infants born at less than 29 weeks gestation with chronic lung disease or those with significant congenital heart disease who have RSV infection are more likely to be hospitalized and have increased morbidity and mortality. Palivizumab (Synagis®, Medimmune) is a humanized monoclonal antibody for the prevention of severe LRTI by RSV in high-risk children. The current use of Palivizumab in Saudi Arabia is not regulated and does not meet approved standards. This clinical practice policy statement was developed by the Ministry of Health and is supported by the National Immunization Technical Advisory Group (NITAG) in Saudi Arabia. It is based on available national and international data on the use of Palivizumab for the prevention of severe LRTI caused by RSV in high-risk pediatric patients. These guidelines were solicited and endorsed by two Saudi societies: The Neonatology and the Pediatric Infectious Diseases Societies.