Association between semi-quantitative microbial load and respiratory symptoms among Thai military recruits: a prospective cohort study

Abstract

BackgroundMultiplex real-time polymerase chain reaction assays have improved diagnostic sensitivity for a wide range of pathogens. However, co-detection of multiple agents and bacterial colonization make it difficult to distinguish between asymptomatic infection or illness aetiology. We assessed whether semi-quantitative microbial load data can differentiate between symptomatic and asymptomatic states for common respiratory pathogens.MethodsWe obtained throat and nasal swab samples from military trainees at two Thai Army barracks. Specimens were collected at the start and end of 10-week training periods (non-acute samples), and from individuals who developed upper respiratory tract infection during training (acute samples). We analysed the samples using a commercial multiplex respiratory panel comprising 33 bacterial, viral and fungal targets. We used random effects tobit models to compare cycle threshold (Ct) value distributions from non-acute and acute samples.ResultsWe analysed 341 non-acute and 145 acute swab samples from 274 participants. Haemophilus influenzae type B was the most commonly detected microbe (77.4% of non-acute and 64.8% of acute samples). In acute samples, nine specific microbe pairs were detected more frequently than expected by chance. Regression models indicated significantly lower microbial load in non-acute relative to acute samples for H. influenzae non-type B, Streptococcus pneumoniae and rhinovirus, although it was not possible to identify a Ct-value threshold indicating causal etiology for any of these organisms.ConclusionsSemi-quantitative measures of microbial concentration did not reliably differentiate between illness and asymptomatic colonization, suggesting that clinical symptoms may not always be directly related to microbial load for common respiratory infections.Electronic supplementary materialThe online version of this article (10.1186/s12879-018-3358-4) contains supplementary material, which is available to authorized users.

Respiratory microbes detected in hospitalized adults with acute respiratory infections: associations between influenza A(H1N1)pdm09 virus and intensive care unit admission or fatal outcome in Vietnam (2015–2017)

“…It is worth remembering that multiplex rPCR also detects the genomes of asymptomatic microbes, persistently infectious viruses, and normal bacterial flora. Therefore, the test does not necessarily signify clinical etiology [ 11 – 14 ]. As an example, a report that analyzed microbes in 312 non-acute specimens from military trainees using the same FTD33 kit showed that viruses and bacteria were present in 13.8 and 93.3% of throat and nasal swabs, respectively, from asymptomatic examinees [ 11 ].…”

“…Therefore, the test does not necessarily signify clinical etiology [ 11 – 14 ]. As an example, a report that analyzed microbes in 312 non-acute specimens from military trainees using the same FTD33 kit showed that viruses and bacteria were present in 13.8 and 93.3% of throat and nasal swabs, respectively, from asymptomatic examinees [ 11 ]. It is difficult to verify the clinical significance of the detected microbes using only multiplex rPCR.…”

“…On the other hand, Influenza viruses are not persistent or latent infections, and are rarely detected in asymptomatic controls [ 11 – 13 ]. Several reports have compared disease severity in hospitalized patients with laboratory-confirmed H1N1pdm and H3 infections [ 22 – 25 , 29 , 30 ].…”

“…Thus, multiple microbes are often detected simultaneously in the same clinical specimen. It is important to understand that the PCR-positive microbes are candidate disease-causing pathogens, but not all are necessarily associated with the particular disease [ 11 – 14 ]. For bacteria and fungi in particular, it is difficult to gauge their relevance to the symptoms.…”

Systematic review on the association between respiratory virus real-time PCR cycle threshold values and clinical presentation or outcomes

“…8,19,36 Across HAdV studies other than Feikin et al, 6 Schjelderup Nilsen et al 37 2019 reported that Ct values <30 were associated with respiratory tract infection (RTI), adjusted for age, gender and presence of other viruses; however, three other studies reported no associations between Ct values and symptom severity, hospitalization or LOS. 8,18,28 Aside from Feikin et al, 6 no further associations were reported across studies with HMPV and PiV, with exception of Fuller et al, 18 in which hospitalized paediatric patients (<5 years old) with PiV reported lower Ct values than controls (P = 0.047), and conversely, HMPV infections had lower Ct values in outpatients versus inpatients (P = 0.030), similar to the outcome for influenza. 8,28,38 In one study of herpes simplex virus (HSV), higher viral load was associated with increased mortality, disease severity and ICU admission; however, there were no other HSV respiratory studies identified in this review.…”