Association of the C_T values of real‐time PCR of viral upper respiratory tract infection with clinical severity, Kenya

Abstract

Quantitative real-time polymerase chain reaction (qRT-PCR) assay of the upper respiratory tract is used increasingly to diagnose lower respiratory tract infections. The cycle threshold (CT ) values of qRT-PCR are continuous, semi-quantitative measurements of viral load, although interpretation of diagnostic qRT-PCR results are often categorized as positive, indeterminate, or negative, obscuring potentially useful clinical interpretation of CT values. From 2008 to 2010, naso/oropharyngeal swabs were collected from outpatients with influenza-like illness, inpatients with severe respiratory illness, and asymptomatic controls in rural Kenya. CT values of positive specimens (i.e., CT values < 40.0) were compared by clinical severity category for five viruses using Mann-Whitney U-test and logistic regression. Among children <5 years old we tested with respiratory syncytial virus (RSV), inpatients had lower median CT values (27.2) than controls (35.8, P = 0.008) and outpatients (34.7, P < 0.001). Among children and older patients infected with influenza virus, outpatients had the lowest median CT values (29.8 and 24.1, respectively) compared with controls (P = 0.193 for children, P < 0.001 for older participants) and inpatients (P = 0.009 for children, P < 0.001 for older participants). All differences remained significant in logistic regression when controlling for age, days since onset, and coinfection. CT values were similar for adenovirus, human metapneumovirus, and parainfluenza virus in all severity groups. In conclusion, the CT values from the qRT-PCR of upper respiratory tract specimens were associated with clinical severity for some respiratory viruses.

The interdependencies of viral load, the innate immune response, and clinical outcome in children presenting to the emergency department with respiratory syncytial virus-associated bronchiolitis

“…In the latter study, sample quality was not measured and therefore could not be corrected by RNase P copy number. Additionally, samples were collected from hospitalized infants only and later into the course of infection compared to the current study [17] Others have reported similar associations between viral load and disease severity, but the associations are weak and come either from hospitalized infants [20–23] or infants healthy enough to stay home [19, 24]–rarely both [26]. Additionally, most of the samples were collected later in the course of infection than those analyzed here.…”

“…Results comparisons are confounded by differences in study design and measurement methods. Most samples have been collected late in infection from hospitalized children [20–23, 25] or from children healthy enough to stay home [19, 24]; and most lack measurements of host response [19–22, 26]. Thus, there is a systematic lack of viral load and host response data, especially from time points early in the course of illness, from young children ultimately experiencing a broad range of disease severity.…”

Evaluation of Viral Diagnostics on rEspiratory iNfections in ChildrEn

“…The incidence of multiple-viral infections in one single patient is reported as high as 14 -44%, depending on different populations and test panels 66 . In a multicentre study, involving 2207 children less than two years of age, the incidence of multiple infections in children hospitalized for bronchiolitis was 30 percent 67 .…”

“…Sommige onderzoekers suggereren een positieve relatie hiertussen [63][64][65][66][67][68][69][70][71][72] , terwijl anderen die relatie niet zien [73][74][75][76][77][78] In de kindergeneeskunde praktijk is virale diagnostiek vaak gebruikt als een enkelvoudige meting bij eerste presentatie van een kind op de spoedeisende hulpafdeling of polikliniek. Deze omstandigheden zijn echter niet optimaal om de relatie tussen viral load en ziekte-ernst te bestuderen, omdat viral load een dynamisch proces is.…”

Viral load in respiratory syncytial virus infected premature newborns under prophylaxis with palivizumab

“…Several laboratory techniques have been used in the diagnosis of HHRSV and among than Real-Time polymerase chain reaction (qPCR) can be used not only to detect the virus, but also to quantify them and try to do a parallel with the severity of HHRSV infection [7].…”