Intra-spinal abscess due to Bacteroides fragilis and Klebsiella pneumoniae co-infection in a child with spinal dysraphism.

Bacteroides fragilis (B. fragilis) is an uncommon cause of spinal abscess. We present a case of an 18-month-old child, with spinal dysraphism-Spina bifida occulta, who developed intra-spinal abscess infection with B. fragilis and Klebsiella pneumoniae. Magnetic resonance imaging (MRI) of the brain and spine showed multiple abscesses extending through the presacral fistula into the spinal cord. Patient was surgically treated along with administration of antimicrobial agents (ceftriaxone and metronidazole), resulting in an excellent clinical outcome.

Early-onset subclinical cardiovascular damage assessed by non-invasive methods in children with Juvenile Idiopathic Arthritis: analytical cross-sectional study.

Chronic inflammation starting early in life and continuing into adulthood may predispose children with Juvenile Idiopathic Arthritis (JIA) to cardiovascular (CV) complications. To compare non-invasive CV risk markers- left ventricular mass index (LVMi), brachial artery flow mediated dilatation (FMD) and carotid artery intima-media thickness (CIMT) between patients with JIA and healthy controls. Measurements of LVMi, CIMT and FMD and lipid profile were compared between 4 and 18 year old 81 patients with JIA and 78 age and sex matched healthy controls. Among 81, 20 had systemic onset, 19 enthesitis related arthritis, 9 polyarticular rheumatoid factor (RF) + ve, 19 polyarticular RF -ve, 11 oligo-articular, and 3 un-differentiated JIA. FMD was significantly lower (p < 0.001), CIMT and LVMi significantly higher in patients (p ≤ 0.001). CIMT showed positive correlation with blood pressure (p = 0.001), disease duration (p ≤ 0.001) and negative correlation with high density lipoprotein (HDL) (p ≤ 0.001). FMD correlated positively with HDL (p = 0.006) and negatively with disease duration (p ≤ 0.001). CIMT (p = 0.017) and FMD (p = 0.04) were significantly worse in active than inactive disease. Children with JIA have worse lipid profile, increased LVMi, CIMT, and reduced brachial artery FMD, suggestive of early cardiovascular dysfunction.

The IRF5 rs2004640 (G/T) polymorphism is not a genetic risk factor for systemic lupus erythematosus in population from south India.

Background & objectives: Genetic aberrations disrupting toll-like receptor and interferon homeostasis enhance the risk of systemic lupus erythematosus (SLE). Raised serum interferon-alpha (IFN-α) levels in SLE patients have been ascribed to polymorphism (rs2004640 G/T) in interferon regulatory factor 5 (IRF5) gene, resulting in enhanced transcript splicing. A positive association between IRF5 polymorphism and SLE risk has been reported in many populations. This study was aimed to find out frequency of IRF5 rs2004640 G/T polymorphism in patients with SLE and healthy controls and to assess its influence on susceptibility, clinical and serological characteristics of SLE. Methods: IRF5 rs2004640 (G/T) polymorphism was analyzed in 300 SLE patients and 460 age and sex matched controls by real-time PCR. Results: The IRF5 rs2004640 (G/T) polymorphism did not confer risk of SLE or influence clinical or serological phenotype. However, the mutant allele conferred a borderline risk to develop thrombocytopenia (odds ratio: 2.05, 95% confidence interval: 0.97-4.3, P=0.06) in patients with SLE. Interpretation & conclusions: Our study revealed that the IRF5 rs2004640 polymorphism was not a risk factor for SLE in population from south India. It may, however, be a useful genetic marker for thrombocytopenia in SLE patients. Although we could not demonstrate susceptibility toward lupus in the presence of IRF5 rs2004640 (G/T) polymorphism, further exploration of the genetic variability of IRF5 may help uncover its pathogenic role in Indian SLE patients.

US Federal Travel Restrictions for Persons with Higher-Risk Exposures to Communicable Diseases of Public Health Concern.

Published guidance recommends controlled movement for persons with higher-risk exposures (HREs) to communicable diseases of public health concern; US federal public health travel restrictions (PHTRs) might be implemented to enforce these measures. We describe persons eligible for and placed on PHTRs because of HREs during 2014-2016. There were 160 persons placed on PHTRs: 142 (89%) involved exposure to Ebola virus, 16 (10%) to Lassa fever virus, and 2 (1%) to Middle East respiratory syndrome coronavirus. Most (90%) HREs were related to an epidemic. No persons attempted to travel; all persons had PHTRs lifted after completion of a maximum disease-specific incubation period or a revised exposure risk classification. PHTR enforced controlled movement and removed risk for disease transmission among travelers who had contacts who refused to comply with public health recommendations. PHTRs are mechanisms to mitigate spread of communicable diseases and might be critical in enhancing health security during epidemics.

Conveyance Contact Investigation for Imported Middle East Respiratory Syndrome Cases, United States, May 2014.

In 2014, the Centers for Disease Control and Prevention conducted conveyance contact investigations for 2 Middle East respiratory syndrome cases imported into the United States, comprising all passengers and crew on 4 international and domestic flights and 1 bus. Of 655 contacts, 78% were interviewed; 33% had serologic testing. No secondary cases were identified.

Fulminant BCG Disease in a 7 Month Old Healthy Male Infant.

A seven month old healthy male infant was brought with papular skin lesions all over the body, which became ulcerative with increasing fever and redness within 1 week duration. On examination, Bacilli Calmette Guerin (BCG) scar was ulcerated with discharge; infant was irritable with tachycardia and tachypnea. Investigations revealed pancytopenia, and acid fast bacilli was positive in skin lesions and at BCG scar site. There was progressive worsening of infant's condition, culminating in death.

First confirmed cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in the United States, updated information on the epidemiology of MERS-CoV infection, and guidance for the public, clinicians, and public health authorities - May 2014.

Since mid-March 2014, the frequency with which cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection have been reported has increased, with the majority of recent cases reported from Saudi Arabia and United Arab Emirates (UAE). In addition, the frequency with which travel-associated MERS cases have been reported and the number of countries that have reported them to the World Health Organization (WHO) have also increased. The first case of MERS in the United States, identified in a traveler recently returned from Saudi Arabia, was reported to CDC by the Indiana State Department of Health on May 1, 2014, and confirmed by CDC on May 2. A second imported case of MERS in the United States, identified in a traveler from Saudi Arabia having no connection with the first case, was reported to CDC by the Florida Department of Health on May 11, 2014. The purpose of this report is to alert clinicians, health officials, and others to increase awareness of the need to consider MERS-CoV infection in persons who have recently traveled from countries in or near the Arabian Peninsula. This report summarizes recent epidemiologic information, provides preliminary descriptions of the cases reported from Indiana and Florida, and updates CDC guidance about patient evaluation, home care and isolation, specimen collection, and travel as of May 13, 2014.

A rare case of congenital insensitivity to pain with anhidrosis.

A 22-month-old girl of consanguineous parents was admitted with a high-grade fever. She was found to have insensitivity to painful stimuli and an absence of perspiration. She also displayed self-mutilating behaviour and was insensitive to cold/hot water on her body. On examination, there was loss of the tip of the tongue, missing teeth, generalised xerosis, and several ulcers at sites of minor trauma. She also had dysplastic nails and digital ulcers. Sensory examination demonstrated a complete lack of awareness of pain and temperature, vibration and fine touch were intact and lacrimation was normal. Differential diagnoses of hereditary sensory and autonomic neuropathy (HSAN), Lesch-Nyhan syndrome, hypohidrotic ectodermal dysplasia and leprosy were considered. Results of routine blood investigations including serum uric acid were normal. On performing clinical exome sequencing, the diagnosis of congenital insensitivity to pain with anhidrosis (CIPA) of autosomal recessive inheritance was confirmed. A novel, predicted to be pathogenic variant detected at exon 16 of the NTRK1 gene resulting in congenital insensitivity to pain with anhidrosis is reported.Abbreviations: CIPA: congenital Insensitivity to pain with anhidrosis; HSAN: hereditary sensory and autonomic neuropathy; NGF: nerve growth factor; NTRK1: neurotrophic tyrosine kinase receptor 1 gene; TrKA: tropomyosin receptor kinase A.

Tuberculosis Disease Among Nonimmigrant Visa Holders Reported to US Quarantine Stations, January 2011-June 2016.

US-bound immigrants and refugees undergo a mandatory overseas medical examination that includes tuberculosis screening; this exam is not routinely required for temporary visitors applying for non-immigrant visas (NIV) to visit, work, or study in the United States. US health departments and foreign ministries of health report tuberculosis cases in travelers to Centers for Disease Control and Prevention Quarantine Stations. We reviewed cases reported to this passive surveillance system from January 2011 to June 2016. Of 1252 cases of tuberculosis in travelers reported to CDC, 114 occurred in travelers with a long-term NIV. Of these, 83 (73%) were infectious; 18 (16%) with multidrug-resistant tuberculosis (MDR TB) and one with extensively drug-resistant tuberculosis (XDR TB). We found evidence that NIV holders are diagnosed with tuberculosis disease in the United States. Given that long-term NIV holders were over-represented in this data set, despite the small proportion (4%) of overall non-immigrant admissions they represent, expanding the US overseas migration health screening program to this population might be an efficient intervention to further reduce tuberculosis in the United States.

Development of a new multiplex PCR to detect fecal coccidian parasite.

BACKGROUND: Cryptosporidium spp., Cystoisospora belli and Cyclospora cayetanensis are common intestinal coccidian parasites causing gastroenteritis. The clinical presentation caused by each parasite is indistinguishable from each other. Uniplex polymerase chain reaction (PCR) for these three groups of intestinal coccidian parasites was developed by us in our laboratory. Thereafter, we planned to develop a single-run multiplex polymerase chain reaction (mPCR) assay to detect Cryptosporidium spp., C. belli and C. cayetanensis simultaneously from a stool sample and described it here as coccidian mPCR. METHODS: New primers for C. belli and C. cayetanensis were designed and uniplex PCRs were standardized. The coccidian mPCR was standardized with known positive DNA control isolates. It was validated with 58 known positive and 58 known negative stool samples, which were previously identified by uniplex PCR. RESULTS: The coccidian mPCR was standardized with earlier primers designed by us for Cryptosporidium spp. and C. cayetanensis, and a newly designed primer for the internal transcribed spacer-1 (ITS-1) gene for C. belli. The coccidian mPCR was 92.1% sensitive for Cryptosporidium spp., and 100% sensitive for C. belli and C. cayetanensis each, when tested on 116 known samples. It was 100% specific for all intestinal coccidian parasites. Two representative PCR products of the newly designed ITS-1 primer for C. belli were sequenced and submitted to the GenBank, which best match with the sequences of C. belli. CONCLUSION: A highly sensitive, specific, cost-effective, indigenous, single-run coccidian mPCR has been developed, which can simultaneously detect Cryptosporidium spp., C. belli and C. cayetanensis.

Normative data for aquagenic wrinkling of palms in children 1-15 years of age: A cross-sectional study.

BACKGROUND: Aquagenic wrinkling of palms (AWP) is emerging as a screening test for cystic fibrosis (CF). There is lack of normative data for the same in our population. OBJECTIVES: To generate normative data for AWP in children 1-15 years of age and to describe the factors associated with it. METHODS: Children aged 1-15 years were enrolled after obtaining informed consent and assent of the parent and child based on age. Information regarding age, gender, anthropometry, indications for visiting hospital and drug intake were noted down. Wrinkling test was done using distilled water maintained in room temperature. Sweat chloride analysis was done using Nano duct sweat analysis system for children having AWP within 3 min. The mean/median time to wrinkle was noted and presented as centile curves after smoothing. RESULTS: The mean (SD) and median (interquartile range [IQR]) aquagenic wrinkling time in children 1-15 years of age was 4.88 (1.066) and 5 (4-5.75) minutes respectively. The mean (SD) and median (IQR) time for AWP was 4.78 (1.076) and 5 (4-5) minutes respectively for boys and 4.98 (1.048) and 5 (4-6) minutes, respectively for girls. The time taken to wrinkle was observed to increase with age. Males have earlier AWP than females. There was no association between AWP and anthropometry or sweat chloride levels. CONCLUSION: We have estimated the normative data for AWP in children 1-15 years of age which can be used for CF screening in children with typical clinical features from resource limited settings.

Pyridoxine Therapy: Not Just the Dose, the Duration Matters Too.

Pyridoxine-dependent epilepsy (PDE) (OMIM 266100) is an autosomal recessive disorder of lysine metabolism secondary to antiquitin deficiency. The prototypical presentation is intractable neonatal seizures that do not respond to conventional antiseizure medication but are well controlled by pyridoxine supplementation. Atypical forms account for one-third of the PDE spectrum and may escape early diagnosis. The common atypical presentations include the prenatal onset of seizures, seizures onset as delayed as 3 years of age, autism, arrested hydrocephalus, and fetal ventriculomegaly. Herein, we describe a 9-month-old child with neonatal-onset refractory seizures who failed two short trials of pyridoxine therapy and was later diagnosed with PDE by molecular studies. Regardless of the therapeutic response, a prolonged course of pyridoxine therapy is justified to identify delayed responders in infants with drug-refractory epilepsy of no apparent etiology.

COVID-19 cases reported in Colorado following screening at selected US airports, January - July 2020.

OBJECTIVE: We sought to estimate the proportion of air travelers who may have been infected with SARS-CoV-2 upon arrival to Colorado by comparing data on Colorado residents screened upon entering the US to COVID-19 cases reported in the state. Data on Colorado's screened passengers arriving into the US between January 17 and July 30, 2020 were compared to Colorado's Electronic Disease Reporting System. We conducted a descriptive analysis of true matches, including age, gender, case status, symptom status, time from arrival to symptom onset (days), and time from arrival to specimen collection date (days). RESULTS: Fourteen confirmed COVID-19 cases in travelers who were diagnosed within 14 days after arriving in Colorado were matched to the 8,272 travelers who underwent screening at 15 designated airports with a recorded destination of Colorado, or 0.2%. Most (N = 13/14 or 93%) of these infected travelers arrived in Colorado in March 2020; 12 (86%) of them were symptomatic. Entry screening for COVID-19 and the sharing of traveler information with the Colorado Department of Public Health and Environment appeared to identify few cases early in the pandemic. Symptom-based entry screening and sharing of traveler information was minimally effective at decreasing travel-associated COVID-19 transmission.

Cross-sectional survey of SARS-CoV-2 testing at US airports and one health department's proactive management of travelers.

BACKGROUND: Many health departments and private enterprises began offering SARS-CoV-2 testing to travelers at US airports in 2020. Persons with positive SARS-CoV-2 test results who have planned upcoming travel may be subject to US federal public health travel restrictions. We assessed availability of testing for SARS-CoV-2 at major US airports. We then describe the management of cases and close contacts at Denver International Airport's testing site. METHODS: We selected 100 US airports. Online surveys were conducted during November-December 2020 and assessed availability of testing for air travelers, flight crew, and airport employees. Respondents included health department (HD) staff or airport directors. We analyzed testing data and management practices for persons who tested positive and their close contacts at one airport (Denver International) from 12/21/2020 to 3/31/2021. RESULTS: Among the 100 selected airports, we received information on 77 airports; 38 (49%) had a testing site and several more planned to offer one (N = 7; 9%). Most sites began testing in the fall of 2020. The most frequently offered tests were RT-PCR or other NAAT tests (N = 28). Denver International Airport offered voluntary SARS-CoV-2 testing. Fifty-four people had positive results among 5724 tests conducted from 12/21/2020 to 3/31/2021 for a total positivity of < 1%. Of these, 15 were travelers with imminent flights. The Denver HD issued an order requiring the testing site to immediately report cases and notify airlines to cancel upcoming flight itineraries for infected travelers and their traveling close contacts, minimizing the use of federal travel restrictions. CONCLUSIONS: As of December 2020, nearly half of surveyed US airports had SARS-CoV-2 testing sites. Such large-scale adoption of airport testing for a communicable disease is unprecedented and presents new challenges for travelers, airlines, airports, and public health authorities. This assessment was completed before the US and other countries began enforcing entry testing requirements; testing at airports will likely increase as travel demand returns and test requirements for travel evolve. Lessons from Denver demonstrate how HDs can play a key role in engaging airport testing sites to ensure people who test positive for SARS-CoV-2 immediately before travel do not travel on commercial aircraft.

Molecular detection of Cystoisospora belli by single-run polymerase chain reaction in stool samples.

INTRODUCTION: Cystoisospora belli (C. belli) is the only pathogenic species of the Cystoisospora genus responsible for severe diarrhea in immunocompromised patients. Most common microscopic method of diagnosis is less sensitive due to intermittent shedding of oocysts. We developed a new single-run polymerase chain reaction (PCR)-based diagnostic assay for C. belli. METHODS: A new single-run PCR-based diagnostic assay was standardized for the detection of C. belli. Diagnostic reproducibility and repeatability of the PCR assay were evaluated. A cross-sectional analytical study was done on a total of 354 stool samples collected from 331 immunocompromised patients with diarrhea. All the stool samples were tested for the presence of oocysts of C. belli and were also tested by our new PCR assay for C. belli. Three of the representative PCR products were confirmed by sequencing. Fisher's exact test was used to compare the two proportions. RESULTS: Microscopy detected C. belli in 11/354 (3.1%) of stool samples, and the new PCR-based assay detected C. belli in 16/354 (4.5%). The new single-run PCR-based assay detected C. belli in all the stool samples which were tested positive by microscopy and additionally detected C. belli in five stool samples. The developed PCR assay detected statistically significant proportion of C. belli (p < 0.001) as compared to microscopy. The 795 base pair PCR product from one microscopy positive stool sample and two microscopy negative stool samples were confirmed by sequencing. CONCLUSION: Our newly developed single-run PCR-based detection assay for C. belli is robust and reproducible. It may be used for molecular diagnosis of cystoisosporiasis especially in transplant, pediatrics, and human immunodeficiency virus (HIV) positive patients.

Association of HLA-G, HLA-E and HLA-B*27 with susceptibility and clinical phenotype of enthesitis related arthritis (ERA).

We studied the association of Enthesitis related arthritis (ERA) the most common variant of juvenile idiopathic arthritis (JIA) in Asians, with HLA-G and -E polymorphisms. HLA-G (14 bp Ins/Del rs371194629, +3142 rs1063320, +3187 rs9380142) and HLA-E (rs1264457, and rs2844724) polymorphisms were analyzed in 127 patients with ERA and 381 ethnically matched healthy controls with TaqMan 5'-nuclease assay using allele-specific fluorogenic oligonucleotide probes. HLA-G and -E polymorphisms were not found to be associated with susceptibility to ERA. HLA-G +3187 (rs9380142) G allele was associated with hip arthritis (Pc = 0.04, OR = 2.22, 95%CI = 1.07-4.63) and hip deformity (Pc = 0.02, OR = 2.51, 95%CI = 1.16-5.43). HLA-B*27 was positive in 91. HLA-E rs1264457 G and rs2844724 T alleles may be associated with B*27 positivity in ERA. Among HLA-G, -E haplotypes, frequency of -InsGAAC was significantly higher in patients than healthy controls (Pc = 0.003). In conclusion, HLA-G and HLA-E haplotype -InsGAAC may be associated with susceptibility to ERA and HLA-G +3187 rs9380142 A>G polymorphism may be a poor prognostic marker for progression to hip arthritis and deformity in ERA-JIA.

Clinical Characteristics, Molecular Profile, and Outcomes in Indian Patients with Glutaric Aciduria Type 1.

Glutaric acidemia type 1 (GA-1, OMIM 231670) is an autosomal recessive inborn error of metabolism caused by the deficiency of glutaryl-coenzyme A (CoA) dehydrogenase with most children presenting in infancy with encephalopathy, dystonia, and macrocephaly. In this article, we presented the clinical characteristics, molecular profile, and outcomes in 29 unrelated families with affected children (30 cases total). The mean age at onset of illness was 10 months (±14.58), whereas the mean age at referral for molecular diagnosis was 29.44 months (±28.11). Patients were residents of nine different states of India. Clinical presentation varied from acute encephalitis followed by neuroregression and chronic/insidious developmental delay. Neurological sequelae varied from asymptomatic (no sequelae, 2 patients) to moderate (5 patients) and severe (23 patients) sequelae. All patients underwent blood tandem mass spectrometry (TMS on dried blood spots) and/or urine gas chromatography mass spectrometry (GCMS). Neuroimaging demonstrated batwing appearance in 95% cases. Sanger's sequencing of GCDH , covering all exons and exon-intron boundaries, was performed for all patients. Variants identified include 15 novel coding variants: p.Met100Thr, p.Gly107Ser, p.Leu179Val, p.Pro217Ser, p. Phe236Leufs*107, p.Ser255Pro, p.Met266Leufs*2, p.Gln330Ter, p.Thr344Ile, p.Leu345Pro, p.Lys377Arg, p.Leu424Pro, p.Asn373Lys, p.Lys377Arg, p.Asn392Metfs*9, and nine known genetic variants such as p.Arg128Gln, p.Leu179Arg, p.Trp225Ter, p.Met339Val, p.Gly354Ser, p.Arg402Gln, p.Arg402Trp, p.His403Tyr, and p.Ala433Val (Ensembl transcript ID: ENST00000222214). Using in silico analysis, genetic variants were shown to be affecting the residues responsible for homotetramer formation of the glutaryl-CoA dehydrogenase protein. Treatment included oral carnitine, riboflavin, protein-restricted diet, lysine-deficient special formulae, and management of acute crises with intravenous glucose and hydration. However, the mortality (9/30, 27.58%) and morbidity was high in our cohort with only two patients affording the diet. Our study is the largest multicentric, genetic variant-proven series of glutaric aciduria type 1 from India till date.

The Seattle Flu Study: a multiarm community-based prospective study protocol for assessing influenza prevalence, transmission and genomic epidemiology.

INTRODUCTION: Influenza epidemics and pandemics cause significant morbidity and mortality. An effective response to a potential pandemic requires the infrastructure to rapidly detect, characterise, and potentially contain new and emerging influenza strains at both an individual and population level. The objective of this study is to use data gathered simultaneously from community and hospital sites to develop a model of how influenza enters and spreads in a population. METHODS AND ANALYSIS: Starting in the 2018-2019 season, we have been enrolling individuals with acute respiratory illness from community sites throughout the Seattle metropolitan area, including clinics, childcare facilities, Seattle-Tacoma International Airport, workplaces, college campuses and homeless shelters. At these sites, we collect clinical data and mid-nasal swabs from individuals with at least two acute respiratory symptoms. Additionally, we collect residual nasal swabs and data from individuals who seek care for respiratory symptoms at four regional hospitals. Samples are tested using a multiplex molecular assay, and influenza whole genome sequencing is performed for samples with influenza detected. Geospatial mapping and computational modelling platforms are in development to characterise the regional spread of influenza and other respiratory pathogens. ETHICS AND DISSEMINATION: The study was approved by the University of Washington's Institutional Review Board (STUDY00006181). Results will be disseminated through talks at conferences, peer-reviewed publications and on the study website (www.seattleflu.org).