scholarly journals Association of the CPT1A p.P479L Metabolic Gene Variant With Childhood Respiratory and Other Infectious Illness in Nunavut

2021 ◽  
Vol 9 ◽  
Author(s):  
Sorcha A. Collins ◽  
Sharon Edmunds ◽  
Gwen Healey Akearok ◽  
J. Robert Thompson ◽  
Anders C. Erickson ◽  
...  

Objective: Infectious illness, including lower respiratory tract infection (LRTI), is a leading cause of childhood morbidity and infant mortality in Inuit children in Nunavut Canada. The carnitine palmitoyltransferase 1A (CPT1A) p.P479L variant is common in arctic Indigenous populations of Alaska, Canada, and Greenland. CPT1A is a fatty acid oxidation enzyme expressed in the liver, immunocytes and other tissues, and is needed to use fats for energy during fasting. Previous association of the variant with early childhood infectious illness and infant death has been challenged because of sample size and limited adjustment for confounders. We evaluated whether the p.P479L variant is associated with infectious illness in Inuit children of Nunavut, Canada.Methods: We conducted a retrospective clinical chart review of 2,225 Inuit children (0–5 years) for infectious illness (including otitis media, gastroenteritis, and hospital admission for LRTI), prenatal, perinatal, and socioeconomic indicators, subsequently linking to CPT1A genotype. Multivariable logistic regression adjusted for birth characteristics, breastfeeding, maternal smoking, food insecurity, and socioeconomic indicators.Results: Overall, 27% of children were hospitalized for LRTI, 86% had otitis media and 50% had gastroenteritis. The p.P479L allele frequency was 0.82. In multivariable analysis, p.P479L homozygosity was associated with LRTI admission (aOR:2.88 95%CI:1.46–5.64), otitis media (aOR:1.83, 95%CI:1.05–3.21), and gastroenteritis (aOR:1.74, 95%CI:1.09–2.77), compared to non-carriers.Conclusion: Children homozygous for the p.P479L variant were more likely to experience infectious illness than non-carriers, including hospitalization for respiratory tract infections. Given the role of CPT1A in immunocytes, our findings indicate that more study is needed to determine if there is a role of the variant in immune response. Continued Inuit involvement is essential when considering next steps.

mBio ◽  
2018 ◽  
Vol 9 (5) ◽  
Author(s):  
Kenneth L. Brockman ◽  
Patrick N. Azzari ◽  
M. Taylor Branstool ◽  
John M. Atack ◽  
Benjamin L. Schulz ◽  
...  

ABSTRACT Biofilms play a critical role in the colonization, persistence, and pathogenesis of many human pathogens. Multiple mucosa-associated pathogens have evolved a mechanism of rapid adaptation, termed the phasevarion, which facilitates a coordinated regulation of numerous genes throughout the bacterial genome. This epigenetic regulation occurs via phase variation of a DNA methyltransferase, Mod. The phasevarion of nontypeable Haemophilus influenzae (NTHI) significantly affects the severity of experimental otitis media and regulates several disease-related processes. However, the role of the NTHI phasevarion in biofilm formation is unclear. The present study shows that the phasevarions of multiple NTHI clinical isolates regulate in vitro biofilm formation under disease-specific microenvironmental conditions. The impact of phasevarion regulation was greatest under alkaline conditions that mimic those known to occur in the middle ear during disease. Under alkaline conditions, NTHI strains that express the ModA2 methyltransferase formed biofilms with significantly greater biomass and less distinct architecture than those formed by a ModA2-deficient population. The biofilms formed by NTHI strains that express ModA2 also contained less extracellular DNA (eDNA) and significantly less extracellular HU, a DNABII DNA-binding protein critical for biofilm structural stability. Stable biofilm structure is critical for bacterial pathogenesis and persistence in multiple experimental models of disease. These results identify a role for the phasevarion in regulation of biofilm formation, a process integral to the chronic nature of many infections. Understanding the role of the phasevarion in biofilm formation is critical to the development of prevention and treatment strategies for these chronic diseases. IMPORTANCE Upper respiratory tract infections are the number one reason for a child to visit the emergency department, and otitis media (middle ear infection) ranks third overall. Biofilms contribute significantly to the chronic nature of bacterial respiratory tract infections, including otitis media, and make these diseases particularly difficult to treat. Several mucosa-associated human pathogens utilize a mechanism of rapid adaptation termed the phasevarion, or phase variable regulon, to resist environmental and host immune pressures. In this study, we assessed the role of the phasevarion in regulation of biofilm formation by nontypeable Haemophilus influenzae (NTHI), which causes numerous respiratory tract diseases. We found that the NTHI phasevarion regulates biofilm structure and critical biofilm matrix components under disease-specific conditions. The findings of this work could be significant in the design of improved strategies against NTHI infections, as well as diseases due to other pathogens that utilize a phasevarion.


Author(s):  
Rajendra Haribhau Dhate

There is availability of number of higher antibiotics, still there is challenge to treat middle ear infection and so its recurrence mostly occurs. Sushrut has already described the treatment of Karnastrava, Putikarna and Krimikarna.2Today every persons lifestyle is changed with food habbit, working hours, type of work & pollution etc., these factors are responsible forupper respiratory tract infections which leads to otitis media ( Karnastrava)1. Sushrut has described the treatment for Karnastrava is guggule dhupan 4. As the guggule is ‘ushna’ acts ‘vatshamak,’ due to ‘tikshna, ushna gun, kaph shamak5. Guggule is also shothhar, Jantughna, Vranashodhan, vranaropan and vednasthapan5, it is used in kaph wat rog’. Dhup of guggule can easily reaches at affected area. This properties of guggule is useful in the management karnastrava.So, here I present a case where a chronic otitis media (KARNASTRAVA) is treated with’ guggule dhup.’


2021 ◽  
Vol 22 (15) ◽  
pp. 7868
Author(s):  
Su Young Jung ◽  
Dokyoung Kim ◽  
Dong Choon Park ◽  
Sung Soo Kim ◽  
Tong In Oh ◽  
...  

Otitis media is mainly caused by upper respiratory tract infection and eustachian tube dysfunction. If external upper respiratory tract infection is not detected early in the middle ear, or an appropriate immune response does not occur, otitis media can become a chronic state or complications may occur. Therefore, given the important role of Toll-like receptors (TLRs) in the early response to external antigens, we surveyed the role of TLRs in otitis media. To summarize the role of TLR in otitis media, we reviewed articles on the expression of TLRs in acute otitis media (AOM), otitis media with effusion (OME), chronic otitis media (COM) with cholesteatoma, and COM without cholesteatoma. Many studies showed that TLRs 1–10 are expressed in AOM, OME, COM with cholesteatoma, and COM without cholesteatoma. TLR expression in the normal middle ear mucosa is absent or weak, but is increased in inflammatory fluid of AOM, effusion of OME, and granulation tissue and cholesteatoma of COM. In addition, TLRs show increased or decreased expression depending on the presence or absence of bacteria, recurrence of disease, tissue type, and repeated surgery. In conclusion, expression of TLRs is associated with otitis media. Inappropriate TLR expression, or delayed or absent induction, are associated with the occurrence, recurrence, chronicization, and complications of otitis media. Therefore, TLRs are very important in otitis media and closely related to its etiology.


CHEST Journal ◽  
2012 ◽  
Vol 141 (4) ◽  
pp. 1063-1073 ◽  
Author(s):  
Philipp Schuetz ◽  
Devendra N. Amin ◽  
Jeffrey L. Greenwald

PEDIATRICS ◽  
1991 ◽  
Vol 87 (2) ◽  
pp. 129-133 ◽  
Author(s):  
Ellen R. Wald ◽  
Nancy Guerra ◽  
Carol Byers

This study was performed to determine the usual duration of community-acquired viral upper respiratory tract infections and the incidence of complications (otitis media/sinusitis) of these respiratory tract infections in infancy and early childhood. Children in various forms of child-care arrangements (home care, group care, and day care) were enrolled at birth and observed for 3 years. Families were telephoned every 2 weeks to record on a standardized form the type and severity of illnesses experienced during the previous interval. Only children remaining in their original child-care group for the entire study period were compared. The mean duration of an upper respiratory tract infection varied between 6.6 days (for 1- to 2-year-old children in home care) and 8.9 days (for children younger than 1 year in day care). The percentage of apparently simple upper respiratory tract infections that lasted more than 15 days ranged from 6.5% (for 1- to 3-year-old children in home care) to 13.1% (for 2- to 3-year-old children in day care). Children in day care were more likely than children in home care to have protracted respiratory symptoms. Of 2741 respiratory tract infections recorded for the 3-year period, 801 (29.2%) were complicated by otitis media. During the first 2 years of life, children in any type of day care were more likely than children in home care to have otitis media as a complication of upper respiratory tract infection. In year 3, the risk of otitis media was similar in all types of child care.


2020 ◽  
Vol 10 (2) ◽  
pp. 359-367
Author(s):  
I. I. Ababii ◽  
L. A. Danilov ◽  
M. K. Maniuc ◽  
P. I. Ababii ◽  
S. S. Ghinda ◽  
...  

Currently, a rise in incidence of polyethological inflammation of the upper respiratory tract mucosa paralleled by altered resident and transient microbiota displaying in many cases increased antibiotic resistance has been noted. Opportunistic microbes play a major role in developing inflammatory process in Pirogov–Waldeyer’s ring. An inflammatory process occurring in the tonsillar lymphatic tissue results in host systemic complications. Fighting against acute and chronic infections of the upper respiratory tract holds the main task in pediatric otorhinolaryngology, as they can consequently elicit the cardiovascular, genitourinary and musculoskeletal complications. The results of studies examining this issue remain very contradictory, which accounted for a need to conduct our study on the territory of Moldova featured with mixed climatic conditions. Here, we wanted to study a role of microbial factor in etiopathogenesis of chronic tonsillitis in children. Bacteriological microbiota data for superficial palatine tonsils were obtained form 608 children subdivided into 5 groups: group I — 333 children with compensated chronic tonsillitis; group II — 87 children with decompensated chronic tonsillitis; group III — 91 children with acute upper respiratory tract infections (comparison group); group IV — 48 children with acute upper respiratory tract infections treated with antibiotic therapy; group V — 49 apparently healthy children (control group). It was found that β-hemolytic streptococcus exerting high sensitivity to virtually all antibiotics groups was detected in 17.4% of children with acute tonsilar inflammatory processes and decompensated defense in the lymphatic pharyngeal ring compared to 3.5% in control group. Streptococcus pneumoniae was isolated in all study groups ranging within 4.8–21.7%, including 14% in apparently healthy children characterized by reduced antibiotics sensitivity. The data obtained suggest that sickly children with acute and chronic upper respiratory tract infections constitute a risk group for developing somatic diseases. The high incidence of Streptococcus pneumoniae indicates a need for performing immunoprophylaxis, use of therapeutic vaccination as a up-to-date, combined approach in treatment of such pediatric cohort.


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