Stringent nonpharmaceutical interventions (NPIs) such as lockdowns and border closures are not currently recommended for pandemic influenza control. New Zealand used these NPIs to eliminate ...coronavirus disease 2019 during its first wave. Using multiple surveillance systems, we observed a parallel and unprecedented reduction of influenza and other respiratory viral infections in 2020. This finding supports the use of these NPIs for controlling pandemic influenza and other severe respiratory viral threats.
Mucosal-associated invariant T (MAIT) cells are innate-like T cells that can detect bacteria-derived metabolites presented on MR1. Here we show, using a controlled infection of humans with live ...Salmonella enterica serovar Paratyphi A, that MAIT cells are activated during infection, an effect maintained even after antibiotic treatment. At the peak of infection MAIT cell T-cell receptor (TCR)β clonotypes that are over-represented prior to infection transiently contract. Select MAIT cell TCRβ clonotypes that expand after infection have stronger TCR-dependent activation than do contracted clonotypes. Our results demonstrate that host exposure to antigen may drive clonal expansion of MAIT cells with increased functional avidity, suggesting a role for specific vaccination strategies to increase the frequency and potency of MAIT cells to optimize effector function.
Corynebacterium species are increasingly recognized as important pathogens in granulomatous mastitis. Currently, there are no published treatment protocols for Corynebacterium breast infections. This ...study describes antimicrobial treatment options in the context of other management strategies used for granulomatous mastitis. Corynebacterium spp. isolated from breast tissue and aspirate samples stored from 2002 to 2013 were identified and determined to the species level using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), 16S RNA sequencing, and rpoB gene targets. The MICs for 12 antimicrobials were performed using Etest for each isolate. Correlations of these with antimicrobial characteristics, choice of antimicrobial, and disease outcome were evaluated. Corynebacterium spp. from breast tissue and aspirate samples were confirmed in 17 isolates from 16 patients. Based on EUCAST breakpoints, Corynebacterium kroppenstedtii isolates (n = 11) were susceptible to seven antibiotic classes but resistant to β-lactam antibiotics. Corynebacterium tuberculostearicum isolates (n = 4) were multidrug resistant. Two nonlipophilic species were isolated, Corynebacterium glucuronolyticum and Corynebacterium freneyi, both of which have various susceptibilities to antimicrobial agents. Short-course antimicrobial therapy was common (median, 6 courses per subject; range, 1 to 9 courses). Patients with C. kroppenstedtii presented with a hot painful breast mass and underwent multiple surgical procedures (median, 4 procedures; range, 2 to 6 procedures). The management of Corynebacterium breast infections requires a multidisciplinary approach and includes culture and appropriate sensitivity testing to guide antimicrobial therapy. Established infections have a poor outcome, possibly because adequate concentrations of some drugs will be difficult to achieve in lipophilic granulomata. Lipophilic antimicrobial therapy may offer a therapeutic advantage. The role of immunotherapy has not been defined.
Enteric fever is a systemic infection caused by Salmonella Typhi or Paratyphi A. In many endemic areas, these serovars co-circulate and can cause multiple infection-episodes in childhood. Prior ...exposure is thought to confer partial, but incomplete, protection against subsequent attacks of enteric fever. Empirical data to support this hypothesis are limited, and there are few studies describing the occurrence of heterologous-protection between these closely related serovars. We performed a challenge-re-challenge study using a controlled human infection model (CHIM) to investigate the extent of infection-derived immunity to Salmonella Typhi or Paratyphi A infection. We recruited healthy volunteers into two groups: naïve volunteers with no prior exposure to Salmonella Typhi/Paratyphi A and volunteers previously-exposed to Salmonella Typhi or Paratyphi A in earlier CHIM studies. Within each group, participants were randomised 1:1 to oral challenge with either Salmonella Typhi (104 CFU) or Paratyphi A (103 CFU). The primary objective was to compare the attack rate between naïve and previously challenged individuals, defined as the proportion of participants per group meeting the diagnostic criteria of temperature of ≥38°C persisting for ≥12 hours and/or S. Typhi/Paratyphi bacteraemia up to day 14 post challenge. The attack-rate in participants who underwent homologous re-challenge with Salmonella Typhi was reduced compared with challenged naïve controls, although this reduction was not statistically significant (12/2744% vs. 12/1963%; Relative risk 0.70; 95% CI 0.41-1.21; p = 0.24). Homologous re-challenge with Salmonella Paratyphi A also resulted in a lower attack-rate than was seen in challenged naïve controls (3/1225% vs. 10/1856%; RR0.45; 95% CI 0.16-1.30; p = 0.14). Evidence of protection was supported by a post hoc analysis in which previous exposure was associated with an approximately 36% and 57% reduced risk of typhoid or paratyphoid disease respectively on re-challenge. Individuals who did not develop enteric fever on primary exposure were significantly more likely to be protected on re-challenge, compared with individuals who developed disease on primary exposure. Heterologous re-challenge with Salmonella Typhi or Salmonella Paratyphi A was not associated with a reduced attack rate following challenge. Within the context of the model, prior exposure was not associated with reduced disease severity, altered microbiological profile or boosting of humoral immune responses. We conclude that prior Salmonella Typhi and Paratyphi A exposure may confer partial but incomplete protection against subsequent infection, but with a comparable clinical and microbiological phenotype. There is no demonstrable cross-protection between these serovars, consistent with the co-circulation of Salmonella Typhi and Paratyphi A. Collectively, these data are consistent with surveillance and modelling studies that indicate multiple infections can occur in high transmission settings, supporting the need for vaccines to reduce the burden of disease in childhood and achieve disease control. Trial registration NCT02192008; clinicaltrials.gov.
Enteric fever, caused by oral infection with typhoidal
serovars, presents as a non-specific febrile illness preceded by an incubation period of 5 days or more. The enteric fever human challenge model ...provides a unique opportunity to investigate the innate immune response during this incubation period, and how this response is altered by vaccination with the Vi polysaccharide or conjugate vaccine. We find that on the same day as ingestion of typhoidal
, there is already evidence of an immune response, with 199 genes upregulated in the peripheral blood transcriptome 12 hours post-challenge (false discovery rate <0.05). Gene sets relating to neutrophils, monocytes, and innate immunity were over-represented (false discovery rate <0.05). Estimating cell proportions from gene expression data suggested a possible increase in activated monocytes 12 hours post-challenge (
= 0.036, paired Wilcoxon signed-rank test). Furthermore, plasma TNF-α rose following exposure (
= 0.011, paired Wilcoxon signed-rank test). There were no significant differences in gene expression (false discovery rate <0.05) in the 12 hours response between those who did and did not subsequently develop clinical or blood culture confirmed enteric fever or between vaccination groups. Together, these results demonstrate early perturbation of the peripheral blood transcriptome after enteric fever challenge and provide initial insight into early mechanisms of protection.
Measles continues to be a public health concern world‐wide. Vulnerable individuals including those in which vaccinations is contraindicated, may be reliant on normal human immunoglobulin (NHIG) ...prophylaxis in an aim to prevent disease. This paper will summarise and discuss a tertiary paediatric hospital's clinical experience and the practicalities of administering intramuscular (IM) NHIG to paediatric patients as per the current measles prophylaxis guidelines in Australia. Following potential exposure within the emergency department, 17 paediatric patients (0–15 years) were recommended IM NHIG for prophylaxis. The dose of NHIG ranged from 0.6 to 15 mL and required multiple (2–8) injections. Two patients required sedation for staff to safely administer the injections. Staff involved with these cases reported administering multiple injections to paediatric patients to be a traumatising experience. They also expressed views that the injection of large volumes via the IM route was an impractical method of administration. Based on this experience, we recommend intravenous immunoglobulin be considered when large volumes of NHIG are recommended intramuscularly.
Summary
Background
Exserohilum species are environmental moulds that can cause skin infection and sinusitis in both normal and immunosuppressed children. This study reviews paediatric cases of ...Exserohilum infection in Queensland, Australia, to identify the spectrum of disease and its clinical course.
Methods
All culture‐positive samples of Exserohilum species in children <18 years of age were identified from the Queensland Health Laboratory database (April 2003‐April 2018). Clinical information was recorded from medical records.
Results
Eleven children were identified, and all had isolated Exserohilum rostratum. The mean age was 7.4 years (range 2.3‐17.8) and 64% female. Four immunocompetent children (36%) had a skin infection (2/4), chronic sinusitis (1/4) or otitis externa (1/4). Seven children (64%) had an underlying oncological diagnosis with E. rostratum causing local skin infection (2/7), invasive rhinosinus disease (3/7) or disseminated infection (2/7). All oncological patients were empirically started on liposomal amphotericin B with addition, or switch, to posaconazole or voriconazole.
Conclusion
Exserohilum rostratum infection of the skin has a favourable course, whereas rhinosinus infection can be rapidly invasive in the immunocompromised child requiring prompt surgical intervention and antifungal therapy. Susceptibility data support empiric use of liposomal amphotericin and/or posaconazole.
Background. To expedite the evaluation of vaccines against paratyphoid fever, we aimed to develop the first human challenge model of Salmonella enterica serovar Paratyphi A infection. Methods. Two ...groups of 20 participants underwent oral challenge with S. Paratyphi A following sodium bicarbonate pretreatment at 1 of 2 dose levels (group 1: 1–5 × 103 colony-forming units CFU and group 2: 0.5–1 × 103 CFU). Participants were monitored in an outpatient setting with daily clinical review and collection of blood and stool cultures. Antibiotic treatment was started when prespecified diagnostic criteria were met (temperature ≥38°C for ≥12 hours and/or bacteremia) or at day 14 postchallenge. Results. The primary study objective was achieved following challenge with 1–5 × 103 CFU (group 1), which resulted in an attack rate of 12 of 20 (60%). Compared with typhoid challenge, paratyphoid was notable for high rates of subclinical bacteremia (at this dose, 11/20 55%). Despite limited symptoms, bacteremia persisted for up to 96 hours after antibiotic treatment (median duration of bacteremia, 53 hours interquartile range, 24–85 hours). Shedding of S. Paratyphi A in stool typically preceded onset of bacteremia. Conclusions. Challenge with S. Paratyphi A at a dose of 1–5 × 103 CFU was well tolerated and associated with an acceptable safety profile. The frequency and persistence of bacteremia in the absence of clinical symptoms was notable, and markedly different from that seen in previous typhoid challenge studies. We conclude that the paratyphoid challenge model is suitable for the assessment of vaccine efficacy using endpoints that include bacteremia and/or symptomatology. Clinical Trials Registration. NCT02100397.
•Osteoarticular infections in children under 5 years old are often culture negative.•The peak incidence of osteoarticular infections was between 12 and 24 months of age.•In this age group K. kingae ...was the most prevalent pathogen.•Many culture-negative cases may be missed cases of Kingella infection.•Routine PCR testing of samples is likely to increase Kingella detection rates.
The Pre-school Osteoarticular Infection (POI) study aimed to describe the burden of disease, epidemiology, microbiology and treatment of acute osteoarticular infections (OAI) and the role of Kingella kingae in these infections.
Information about children 3–60 months of age who were hospitalized with an OAI to 11 different hospitals across Australia and New Zealand between January 2012 and December 2016 was collected retrospectively.
A total of 907 cases (73%) were included. Blood cultures grew a likely pathogen in only 18% (140/781). The peak age of presentation was 12 to 24 months (466/907, 51%) and Kingella kingae was the most frequently detected microorganism in this age group (60/466, 13%). In the majority of cases, no microorganism was detected (517/907, 57%). Addition of PCR to culture increased detection rates of K. kingae. However, PCR was performed infrequently (63/907, 7%).
This large multi-national study highlights the need for more widespread use of molecular diagnostic techniques for accurate microbiological diagnosis of OAI in pre-school aged children. The data from this study supports the hypothesis that a substantial proportion of pre-school aged children with OAI and no organism identified may in fact have undiagnosed K. kingae infection. Improved detection of Kingella cases is likely to reduce the average length of antimicrobial treatment.
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