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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.
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Antibacterianos , Infecciones por Flavobacteriaceae , Centros de Atención Terciaria , Humanos , Arabia Saudita/epidemiología , Masculino , Femenino , Estudios Retrospectivos , Adulto , Persona de Mediana Edad , Niño , Incidencia , Infecciones por Flavobacteriaceae/epidemiología , Infecciones por Flavobacteriaceae/tratamiento farmacológico , Infecciones por Flavobacteriaceae/microbiología , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , Adolescente , Adulto Joven , Preescolar , Pruebas de Sensibilidad Microbiana , Mortalidad Hospitalaria , Anciano , Infección Hospitalaria/epidemiología , Infección Hospitalaria/microbiología , Infección Hospitalaria/tratamiento farmacológico , Lactante , Chryseobacterium/efectos de los fármacosRESUMEN
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.
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COVID-19 , Hospitalización , Infecciones por Virus Sincitial Respiratorio , Humanos , COVID-19/epidemiología , Infecciones por Virus Sincitial Respiratorio/epidemiología , Estudios Retrospectivos , Femenino , Masculino , Arabia Saudita/epidemiología , Lactante , Preescolar , Hospitalización/estadística & datos numéricos , Niño , SARS-CoV-2 , Adolescente , Prevalencia , Recién Nacido , Virus Sincitial Respiratorio Humano/aislamiento & purificación , PandemiasRESUMEN
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.
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COVID-19 , Hospitalización , SARS-CoV-2 , Centros de Atención Terciaria , Humanos , Femenino , Arabia Saudita/epidemiología , COVID-19/epidemiología , COVID-19/virología , Masculino , Adulto , SARS-CoV-2/genética , Estudios Retrospectivos , Persona de Mediana Edad , Centros de Atención Terciaria/estadística & datos numéricos , Hospitalización/estadística & datos numéricos , Estaciones del AñoRESUMEN
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.
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Aborto Espontáneo , COVID-19 , Recién Nacido , Embarazo , Femenino , Humanos , Adulto , COVID-19/epidemiología , Estudios Prospectivos , SARS-CoV-2 , Estudios de CohortesRESUMEN
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.
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Infecciones por Bacterias Gramnegativas/epidemiología , Infecciones por Bacterias Gramnegativas/mortalidad , Stenotrophomonas maltophilia/inmunología , Adolescente , Antibacterianos , Infecciones Relacionadas con Catéteres , Niño , Preescolar , Infección Hospitalaria , Femenino , Humanos , Lactante , Unidades de Cuidados Intensivos , Masculino , Pruebas de Sensibilidad Microbiana , Neutropenia , Estudios Retrospectivos , Factores de Riesgo , Arabia SauditaRESUMEN
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.
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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.
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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.
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Exoma , Enfermedades Genéticas Congénitas/diagnóstico , Enfermedades Genéticas Congénitas/epidemiología , Genoma Humano , Consanguinidad , Femenino , Pruebas Genéticas , Secuenciación de Nucleótidos de Alto Rendimiento , Homocigoto , Humanos , Masculino , Anotación de Secuencia Molecular , Morbilidad , Mutación , Fenotipo , Reproducibilidad de los Resultados , Arabia Saudita/epidemiología , Análisis de Secuencia de ADNRESUMEN
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.
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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.
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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.
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Anemia de Células Falciformes/inmunología , Anticuerpos Antibacterianos/sangre , Vacunas Neumococicas/inmunología , Vacunas Conjugadas/inmunología , Adolescente , Anticuerpos Antibacterianos/inmunología , Niño , Femenino , Humanos , Inmunización Secundaria , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Masculino , Fagocitosis/inmunología , Infecciones Neumocócicas/inmunología , Infecciones Neumocócicas/prevención & control , Streptococcus pneumoniae/inmunologíaAsunto(s)
Antirretrovirales/uso terapéutico , Quimioprevención/métodos , Transmisión de Enfermedad Infecciosa/prevención & control , Infecciones por VIH/prevención & control , Infecciones por VIH/transmisión , Profilaxis Posexposición/métodos , Reacción a la Transfusión , Anemia de Células Falciformes/terapia , Niño , ADN Viral/sangre , Femenino , VIH/aislamiento & purificación , Anticuerpos Anti-VIH/sangre , Antígenos VIH/sangre , Humanos , ARN Viral/sangreRESUMEN
BACKGROUND: In the initial description of Middle East respiratory syndrome coronavirus (MERS-CoV) infection, many affected patients were adults with underlying medical comorbidities. Data on the clinical presentation and outcome of pediatric cases are lacking. We report the clinical presentation and outcome of MERS-CoV infection in 11 pediatric patients. METHODS: The clinical presentation, demographic and laboratory data of pediatric patients with MERS-CoV were analyzed. RESULTS: A total of 11 pediatric cases that tested positive by screening and confirmatory polymerase chain reaction for MERS-CoV were reported from Saudi Arabia. Two patients were symptomatic and the other 9 cases were asymptomatic. The median age of patients was 13 (range 2-16) years. There were 8 females and 3 males (2.7:1 ratio). One symptomatic patient died and the other symptomatic patient recovered. The diagnosis of patients was based on positive nasopharyngeal swabs on 10 patients. CONCLUSIONS: MERS-CoV disease is not limited to adults. Most cases of childhood MERS-CoV infection were asymptomatic and tested positive during contact investigation of older patients. Severe disease can occur in children with underlying conditions.
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Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/diagnóstico , Coronavirus del Síndrome Respiratorio de Oriente Medio , Nasofaringe/virología , Adolescente , Enfermedades Asintomáticas , Niño , Preescolar , Infecciones por Coronavirus/virología , Tos/virología , Resultado Fatal , Femenino , Fiebre/virología , Humanos , Masculino , Insuficiencia Respiratoria/virologíaRESUMEN
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.
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Infecciones por Coronavirus/genética , Coronavirus/genética , Brotes de Enfermedades , Evolución Molecular , Genoma Viral , Infecciones del Sistema Respiratorio/genética , Secuencia de Bases , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/transmisión , Amplificación de Genes , Humanos , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/transmisión , Arabia Saudita/epidemiología , SíndromeRESUMEN
BACKGROUND: Middle East respiratory syndrome (MERS) is a new human disease caused by a novel coronavirus (CoV). Clinical data on MERS-CoV infections are scarce. We report epidemiological, demographic, clinical, and laboratory characteristics of 47 cases of MERS-CoV infections, identify knowledge gaps, and define research priorities. METHODS: We abstracted and analysed epidemiological, demographic, clinical, and laboratory data from confirmed cases of sporadic, household, community, and health-care-associated MERS-CoV infections reported from Saudi Arabia between Sept 1, 2012, and June 15, 2013. Cases were confirmed as having MERS-CoV by real-time RT-PCR. FINDINGS: 47 individuals (46 adults, one child) with laboratory-confirmed MERS-CoV disease were identified; 36 (77%) were male (male:female ratio 3·3:1). 28 patients died, a 60% case-fatality rate. The case-fatality rate rose with increasing age. Only two of the 47 cases were previously healthy; most patients (45 [96%]) had underlying comorbid medical disorders, including diabetes (32 [68%]), hypertension (16 [34%]), chronic cardiac disease (13 [28%]), and chronic renal disease (23 [49%]). Common symptoms at presentation were fever (46 [98%]), fever with chills or rigors (41 [87%]), cough (39 [83%]), shortness of breath (34 [72%]), and myalgia (15 [32%]). Gastrointestinal symptoms were also frequent, including diarrhoea (12 [26%]), vomiting (ten [21%]), and abdominal pain (eight [17%]). All patients had abnormal findings on chest radiography, ranging from subtle to extensive unilateral and bilateral abnormalities. Laboratory analyses showed raised concentrations of lactate dehydrogenase (23 [49%]) and aspartate aminotransferase (seven [15%]) and thrombocytopenia (17 [36%]) and lymphopenia (16 [34%]). INTERPRETATION: Disease caused by MERS-CoV presents with a wide range of clinical manifestations and is associated with substantial mortality in admitted patients who have medical comorbidities. Major gaps in our knowledge of the epidemiology, community prevalence, and clinical spectrum of infection and disease need urgent definition. FUNDING: None.
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Infecciones por Coronavirus/epidemiología , Coronavirus/aislamiento & purificación , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Aspartato Aminotransferasas/análisis , Niño , Infecciones Comunitarias Adquiridas/mortalidad , Infecciones Comunitarias Adquiridas/patología , Infecciones Comunitarias Adquiridas/virología , Infecciones por Coronavirus/mortalidad , Infección Hospitalaria/mortalidad , Infección Hospitalaria/patología , Infección Hospitalaria/virología , Diarrea/virología , Femenino , Fiebre/patología , Humanos , L-Lactato Deshidrogenasa/análisis , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Arabia Saudita/epidemiología , Trombocitopenia/patología , Adulto JovenRESUMEN
Autosomal recessive interleukin (IL)-12 p40 (IL-12p40) deficiency is a rare genetic etiology of mendelian susceptibility to mycobacterial disease (MSMD). We report the genetic, immunologic, and clinical features of 49 patients from 30 kindreds originating from 5 countries (India, Iran, Pakistan, Saudi Arabia, and Tunisia). There are only 9 different mutant alleles of the IL12B gene: 2 small insertions, 3 small deletions, 2 splice site mutations, and 1 large deletion, each causing a frameshift and leading to a premature stop codon, and 1 nonsense mutation. Four of these 9 variants are recurrent, affecting 25 of the 30 reported kindreds, due to founder effects in specific countries. All patients are homozygous and display complete IL-12p40 deficiency. As a result, the patients lack detectable IL-12p70 and IL-12p40 and have low levels of interferon gamma (IFN-γ). The clinical features are characterized by childhood onset of bacille Calmette-Guérin (attenuated Mycobacterium bovis strain) (BCG) and Salmonella infections, with recurrences of salmonellosis (36.4%) more common than recurrences of mycobacterial disease (25%). BCG vaccination led to BCG disease in 40 of the 41 patients vaccinated (97.5%). Multiple mycobacterial infections were rare, observed in only 3 patients, whereas the association of salmonellosis and mycobacteriosis was observed in 9 patients. A few other infections were diagnosed, including chronic mucocutaneous candidiasis (n = 3), nocardiosis (n = 2), and klebsiellosis (n = 1). IL-12p40 deficiency has a high but incomplete clinical penetrance, with 33.3% of genetically affected relatives of index cases showing no symptoms. However, the prognosis is poor, with mortality rates of up to 28.6%. Overall, the clinical phenotype of IL-12p40 deficiency closely resembles that of interleukin 12 receptor ß1 (IL-12Rß1) deficiency. In conclusion, IL-12p40 deficiency is more common than initially thought and should be considered worldwide in patients with MSMD and other intramacrophagic infectious diseases, salmonellosis in particular.
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Subunidad p40 de la Interleucina-12/deficiencia , Subunidad p40 de la Interleucina-12/genética , Infecciones por Mycobacterium no Tuberculosas/genética , Infecciones por Salmonella/genética , Adolescente , Adulto , Edad de Inicio , Asia Occidental/epidemiología , Niño , Preescolar , Estudios de Cohortes , Análisis Mutacional de ADN , Femenino , Efecto Fundador , Predisposición Genética a la Enfermedad , Humanos , Lactante , Masculino , Infecciones por Mycobacterium no Tuberculosas/inmunología , Infecciones por Mycobacterium no Tuberculosas/mortalidad , Penetrancia , Análisis de Supervivencia , Túnez/epidemiología , Adulto JovenRESUMEN
BACKGROUND AND OBJECTIVES: The use of a potent combination of antiretroviral (ARV) drugs, so-called highly active ARV therapy (HAART), has dramatically improved the quality of life and overall survival of children with human immunodeficiency virus (HIV) infection. However, these benefits can be compromised by the development of drug resistance. Our objectives were to analyze the prevalence and pattern of HIV-drug resistance among HIV-infected children failing first-line HAART. DESIGN AND SETTING: Retrospective study based on data obtained from July 2006 through January 2009 of prevalence of genotypic resistance estimated in HAART-treated children who experienced virologic failure (HIV RNA > 1000 copies/mL) at a tertiary care center in Riyadh. PATIENTS AND METHODS: The characteristics of the study population and genotype resistance data were analyzed in ARV-treated children who experience virologic failure. RESULTS: Among 22 children who underwent resistance testing, the prevalence of resistance to any drug was 86.4%. Inadequate adherence to ARVs in children with drug resistance was 91%. Twenty-four mutations were detected within the protease coding region and 14 in the reverse transcriptase (RT) coding region. In 80% of isolates piM36I was detected, while rtM184V was detected in 70% of the isolates and was associated with cross-resistance to at least two nucleoside RT inhibitors (NRTI). Clinically significant non-nucleoside RT inhibitors (NNRTI) resistance was conferred by rtK103N. The best ARV susceptibility was to lopinavir in the PI class. ARV resistance was not associated with geographic regions or the CDC classification status. Study children responded satisfactorily to genotype-guided treatment and intensive family counseling. CONCLUSION: ARVs resistance is common among HIV-infected Saudi children who experienced virologic failure to HAART. Inadequate adherence is a common cause for resistance to ARVs in children. Mutations M36I and M184V were more frequent for PIs, NRTIs and NNRTIs. Evaluation of genotype tests should be considered in all children with therapeutic failure to guide future selection of ARV regimens. These data will help improve clinical management of HIV-infected children in Saudi Arabia.