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Summary: Human adenovirus (HAdV) infection can result in a severe respiratory disease. The aim of this study was to identify HAdV types detected in patients hospitalized for severe respiratory illness. The study population consisted of 743 patients with severe respiratory disease admitted to four major hospitals in Kuwait between January 2013 and December 2016. Respiratory specimens were retrospectively screened for 20 respiratory viruses by real-time PCR. The HAdV hexon gene was amplified and directly sequenced, and HAdV types were identified by performing Bayesian phylogenetic analysis. HAdV DNA was detected in 27 (3.6%) patients, with peaks in November and March. Most patients were infants and young children suffering from pneumonia or acute bronchiolitis. The detected HAdV types were C1, C2, C5, B3, and B7. Clusters of HAdV C1, C2, and C5 were observed with high posterior probability. All patients infected with HAdV C5 and 50% of patients infected with HAdV C2 or B7 were admitted to the intensive care unit (ICU). Co-infection with other viruses was detected in 44.4% of patients. The most common co-infecting virus was rhinovirus (HRV). HAdV/HRV co-infection was detected in two children who presumably developed disseminated HAdV infection and died. This is the first report describing the circulation of HAdV types associated with severe outcomes in Kuwait. These findings highlight the need for a national surveillance system to monitor changes in predominant HAdV types and increased numbers of severe respiratory infections.

Kit used: FTD Respiratory pathogens 21
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Background Influenza A(H1N1)pdm09 virus infections often manifest severe respiratory symptoms, particularly in patients with a past history of allergic disease. Most of these findings were reported during the 2009 pandemic. The purpose of this study was to detail the clinical characteristics of influenza virus-induced lower respiratory infection (LRI) during the A(H1N1)pdm09-predominant 2015–2016 season. Methods We retrospectively reviewed the clinical characteristics of influenza-induced LRI cases in children admitted to a tertiary children's hospital. Molecular diagnostic evaluation was performed on samples obtained from the most severe cases. Results We identified 66 patients with influenza-associated hospitalization and included 21 patients with influenza virus-induced LRI for analyses. Twelve patients (57%) were admitted to the pediatric intensive care unit, seven (33%) required mechanical ventilation, and three (14%) required extracorporeal membrane oxygenation. Plastic bronchitis (PB) was identified in six patients (29%), among whom a past medical history of asthma or food allergy were noted in all six patients. A past history of allergic disease was more common among patients with, than among those without, PB (p = 0.009). A(H1N1)pdm09 was detected from all the PB cases, and phylogenetic analyses of the hemagglutinin and neuraminidase genes demonstrated that this virus belonged to subclades 6B.1 and 6B.2. In the six PB cases, we found one patient with H275Y mutation in neuraminidase. Conclusion Allergic disease was a risk factor for developing PB due to influenza A(H1N1)pdm09 infection during the 2015–16 season.

Kit used: FTD Respiratory pathogens 21
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Background: Live respiratory syncytial virus (RSV) candidate vaccine LIDΔM2-2 is attenuated by deletion of the RSV RNA regulatory protein M2-2, resulting in upregulated viral gene transcription and antigen expression but reduced RNA replication.

Methods: RSV-seronegative children ages 6–24 months received a single intranasal dose of 105 plaque forming units (PFU) of LIDΔM2-2 (n = 20) or placebo (n = 9) (NCT02237209, NCT02040831). RSV serum antibodies, vaccine infectivity, and reactogenicity were assessed. During the following RSV season, participants were monitored for respiratory illness and pre- and post-RSV season serum antibodies.

Results: Vaccine virus was shed by 95% of vaccinees (median peak titers of 3.8 log10 PFU/mL by quantitative culture and 6.3 log10 copies/mL by PCR); 90% had ≥4-fold rise in serum neutralizing antibodies. Respiratory symptoms and fever were common in vaccine (95%) and placebo (78%). One vaccinee had grade 2 rhonchi concurrent with vaccine shedding, rhinovirus, and enterovirus. Eight of 19 vaccinees versus 2 of 9 placebo recipients had substantially increased RSV antibody titers after the RSV season without medically attended RSV disease, indicating anamnestic vaccine responses to wild-type RSV without significant illness.

Conclusion: LIDΔM2-2 had excellent infectivity and immunogenicity, encouraging further study of vaccine candidates attenuated by M2-2 deletion.

Kit used: FTD FTD Respiratory pathogens 21
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Objective: To determine the feasibility of a randomised controlled trial (RCT) of rhinothermy for the common cold.
Design: Open label, randomised, controlled feasibility study.
Setting: Single-centre research institute in New Zealand recruiting participants from the community.
Participants: 30 adult participants with symptoms of a common cold, presenting within 48 hours of the onset of symptoms.
Interventions: Participants were randomly assigned 2:1 to receive either 35 L/min of 100% humidified air at 41°C via high flow nasal cannulae, 2 hours per day for up to 5 days (rhinothermy), or vitamin C 250 mg daily for 5 days (control).
Primary and secondary outcome measures: The primary outcome was the proportion of screened candidates who were randomised.
Secondary outcomes included: proportion of randomised participants who completed the study; modified Jackson scores from randomisation to 10 days after initiation of randomised regimen; time until feeling ‘a lot better’ compared with study entry; time until resolution of symptoms or symptom score at 10 days postrandomisation; proportion of organisms identified by PCR analysis of nasal swabs taken at baseline; the patterns of use of the rhinothermy device; estimated adherence of the control group; and rhinothermy device tolerability.
Results: In all 30/79 (38%, 95% CI 27% to 50%) of potential participants screened for eligibility were randomised. Rhinothermy was well tolerated, and all randomised participants completed the study (100%, 95% CI 88% to 100%). The reduction from baseline in the modified Jackson score was greater with rhinothermy compared with control at days 2, 3, 4, 5 and 6, with the maximum difference at day 4 (−6.4, 95% CI −9.4 to −3.3). The substantial clinical benefit threshold for modified Jackson score was a 5-unit change.
Conclusions: This study shows that an RCT of rhinothermy compared with low-dose vitamin C in the treatment of the common cold is feasible.

Kit used: FTD Respiratory pathogens 21

Summary: Respiratory syncytial virus (RSV) is the most important cause of severe acute respiratory tract infection in young children. Alere i RSV is a novel molecular rapid test which identifies respiratory syncytial virus. The group evaluated the clinical performance of the Alere i RSV assay in a pediatric point-of-care setting during winter season 2016 / 2017. Test results from 518 nasopharyngeal swab samples were compared to FTD Respiratory pathogens 21 seen as reference standard. The overall sensitivity and specificity of the Alere i RSV test assay was 93% (CI95 89% – 96%) and 96% (CI95 93% – 98%), respectively. An optimal sensitivity of 98% (CI95 94% - 100%) and specificity of 96% (CI95 90% - 99%) was obtained in children < 6 months. In children ≥ 2 years, sensitivity and specificity remained at 87% (CI95 73% – 96%) and 98% (CI95 92% – 100%), respectively. False negative Alere i RSV test results mostly occurred in samples with low viral load (mean CT value 31.1; CI95 29.6 – 32.6).

Tables: https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-017-2855-1

Kit used: FTD Respiratory pathogens 21

Summary: Mortality from acute bacterial meningitis (ABM) in sub-Saharan African adults and adolescents exceeds 50%. This group tested if Goal Directed Therapy (GDT) was feasible for adults and adolescents with clinically suspected ABM in Malawi.

Sequential patient cohorts of adults and adolescents with clinically suspected ABM were recruited in the emergency department of a teaching hospital in Malawi using a before/after design. Routine care was monitored in year one (P1). In year two (P2), nurses delivered protocolised GDT (rapid antibiotics, airway support, oxygenation, seizure control and fluid resuscitation) to a second cohort. The primary endpoint was composite mean number of clinical goals attained. Secondary endpoints were individual goals attained and death or disability from proven or probable ABM at day 40.

563 patients with suspected ABM were enrolled in the study; 273 were monitored in P1; 290 patients with suspected ABM received GDT in P2. 61% were male, median age 33 years and 90% were HIV co-infected. ABM was proven or probable in 132 (23%) patients. GDT attained more clinical goals compared to routine care: composite mean number of goals in P1 was 0·55 vs. 1·57 in P2 GDT (p<0·001); Death or disability by day 40 from proven or probable ABM occurred in 29/57 (51%) in P1 and 38/60 (63%) in P2 (p = 0·19).

Kit used: FTD Bacterial meningitis

Summary: Acute Encephalitis Syndrome has heralded the emergence of multiple virulent pathogens, which may result in severe morbidity and mortality. In India, encephalitis is not notified and there has been a dearth of analysis for trends in encephalitis death rates and causation. A downward trend has been observed in encephalitis deaths, due to ‘known’ causes, which can be largely explained by improvement in diagnostic, treatment, and prevention methods. There is still a very high proportion of encephalitis deaths in developing countries, where the aetiological diagnosis of the pathogen is not established and thus, lies the importance of monitoring encephalitis morbidity and mortality with a view to improve pathogen diagnosis and identify emerging infectious diseases.

The aim of the study was to formulate a diagnostic approach to viral acute encephalitis syndrome in paediatric age group. A cross-sectional study including 50 paediatric patients, clinically diagnosed with acute encephalitis syndrome using WHO criteria was conducted. The CSF of all the patients was evaluated to diagnose the aetiology for viral pathogens. ELISA was used for diagnosing Japanese encephalitis and dengue encephalitis; and multiplex real time PCR was used for detecting HSV-1, HSV-2, Varicella zoster virus, Mumps virus, Enterovirus and Parechovirus (FTD Viral meningitis).

Confirmed diagnosis was established in 11 (22%) of 50 cases. A confirmed or probable viral agent of encephalitis was found in 7 (14%), bacterial agent was found in 2 (4%), non-infectious aetiology was found in 2 (4%). Fatal outcome was independently associated with patient age.

Despite extensive testing, the aetiologies of more than three fourth of the cases remains elusive. Nevertheless the result from the present study may be useful for future design of early diagnosis and treatment of the disease. New strategies for pathogen identification and continued analysis of clinical features and case histories should help us improve our ability to diagnose, treat and prevent encephalitis.

Overall, the multiplex assay accommodates lower costs and faster turn-around times for the detection of common pathogens found in CSF. The sensitivity and specificity of FTD Viral meningitis surpasses that of culturing techniques. It has shown comparable sensitivity to the singleplex Light cycler assays and improved ability to distinguish HSV-1 and HSV-2.

Kit used: FTD Viral meningitis

Summary: A resurgence of pertussis or whooping cough has been observed worldwide despite broad vaccination coverage. Pertussis like illness (PLI) refers to a clinical syndrome compatible with pertussis infection but lacking laboratory confirmation or an epidemiological link to a confirmed case. Our study aimed to estimate the contribution of Bordetella pertussis infection and identifying predictors of its diagnosis in a cohort of children with PLI. Demographic and clinical information were retrospectively collected from the medical records of children < 13 years old and hospitalized for PLI in two pediatric units in Oman from 1 January 2012 to 31 December 2013. The laboratory data of all cases were reviewed and confirmed cases of pertussis were identified, analyzed, and compared with non-confirmed cases.A total of 131 patients were enrolled in this study. The majority (95.4% [125/131]) were infants. Only 54.1% (71/131) of admitted children with PLI were tested for pertussis. The incidence of pertussis infection among the tested group was 16.9% (12/71) with a 95% confidence interval 8.2−25.6. Severe illness occurred in 56.4% (74/131) of patients, and six were confirmed to have pertussis. Pediatric intensive care unit admission was required for one confirmed case of pertussis and eight cases from the PLI group (three were negative for pertussis, and five were not tested). Receiver operator characteristic curve analysis revealed that a white blood cell count 3 23.5 × 109/L had 96.6% specificity and lymphocytes 3 17 × 109/L had 98.3% specificity. Taking into consideration that the number tested for pertussis was limited, the incidence of pertussis was 16.9% (12 out of 71 patients). Lymphocytosis can be used as a reliable predictor for the diagnosis of pertussis especially in the absence of specific confirmatory tests or until their results are available.

Kit used: FTD Respiratory pathogens 21