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The article discusses the challenges of determining the cause of fever in a child returning from international travel, emphasizing the importance of a detailed travel history in guiding appropriate investigations. Topics include the increasing international travel by Australian residents, the prevalence of serious imported infections in returned child travelers, and an approach to assessing post-travel fever in children, with a focus on common causes such as malaria, dengue, and enteric fever.

With the global rise in antimicrobial resistance, there has been a renewed interest in the application of therapeutic phages to treat bacterial infections. Therapeutic phage monitoring (TPM) is proposed as an essential element of phage therapy (PT) protocols to generate data and fill knowledge gaps regarding the in vivo efficacy of therapeutic phages, patients' immune responses to PT, and the wider ecological effects of PT. By monitoring phage concentrations in blood and tissues, together with immune responses and possible ecological changes during PT, TPM may enable the optimization of dosing and the implementation of precision medicine approaches. Furthermore, TPM can validate diagnostic surrogates of efficacy, direct research efforts, and establish quality assurance indicators for therapeutic phage products. Thus, TPM holds great potential for enhancing our understanding of the multidirectional phage–bacteria–host interactions and advancing "best practice" PT, ultimately improving patient care. [ABSTRACT FROM AUTHOR]

The clinical manifestations of infection with human parechoviruses (HPeVs), members of the family Picornaviridiae, are often indistinguishable from those caused by human enterovirus infections. Over the past decade, outbreaks of [...]

Background Nontuberculous Mycobacterium infections, particularly Mycobacterium abscessus , are increasingly common among patients with cystic fibrosis and chronic bronchiectatic lung diseases. Treatment is challenging due to intrinsic antibiotic resistance. Bacteriophage therapy represents a potentially novel approach. Relatively few active lytic phages are available and there is great variation in phage susceptibilities among M. abscessus isolates, requiring personalized phage identification. Methods Mycobacterium isolates from 200 culture-positive patients with symptomatic disease were screened for phage susceptibilities. One or more lytic phages were identified for 55 isolates. Phages were administered intravenously, by aerosolization, or both to 20 patients on a compassionate use basis and patients were monitored for adverse reactions, clinical and microbiologic responses, the emergence of phage resistance, and phage neutralization in serum, sputum, or bronchoalveolar lavage fluid. Results No adverse reactions attributed to therapy were seen in any patient regardless of the pathogen, phages administered, or the route of delivery. Favorable clinical or microbiological responses were observed in 11 patients. Neutralizing antibodies were identified in serum after initiation of phage delivery intravenously in 8 patients, potentially contributing to lack of treatment response in 4 cases, but were not consistently associated with unfavorable responses in others. Eleven patients were treated with only a single phage, and no phage resistance was observed in any of these. Conclusions Phage treatment of Mycobacterium infections is challenging due to the limited repertoire of therapeutically useful phages, but favorable clinical outcomes in patients lacking any other treatment options support continued development of adjunctive phage therapy for some mycobacterial infections. [ABSTRACT FROM AUTHOR]

The reality of climate change and biodiversity collapse is irrefutable in the 21st century, with urgent action required not only to conserve threatened species but also to protect human life and wellbeing. This existential threat forces us to recognise that our existence is completely dependent upon well-functioning ecosystems that sustain the diversity of life on our planet, including that required for human health. By synthesising data on the ecology, epidemiology and evolutionary biology of various pathogens, we are gaining a better understanding of factors that underlie disease emergence and spread. However, our knowledge remains rudimentary with limited insight into the complex feedback loops that underlie ecological stability, which are at risk of rapidly unravelling once certain tipping points are breached. In this paper, we consider the impact of climate change and biodiversity collapse on the ever-present risk of infectious disease emergence and spread. We review historical and contemporaneous infectious diseases that have been influenced by human environmental manipulation, including zoonoses and vector- and water-borne diseases, alongside an evaluation of the impact of migration, urbanisation and human density on transmissible diseases. The current lack of urgency in political commitment to address climate change warrants enhanced understanding and action from paediatricians - to ensure that we safeguard the health and wellbeing of children in our care today, as well as those of future generations. [ABSTRACT FROM AUTHOR]

Adjunctive phage therapy was used in an attempt to avoid catastrophic outcomes from extensive chronic Pseudomonas aeruginosa osteoarticular infection in a 7‐year‐old child. Monitoring of phage and bacterial kinetics allowed real‐time phage dose adjustment, and along with markers of the human host response, indicated a significant therapeutic effect within two weeks of starting adjunctive phage therapy. These findings strongly suggested the release of bacterial cells or cell fragments into the bloodstream from deep bony infection sites early in treatment. This was associated with transient fever and local pain and with evidence of marked upregulation of innate immunity genes in the host transcriptome. Adaptive immune responses appeared to develop after a week of therapy and some immunomodulatory elements were also observed to be upregulated. SYNOPSIS: Successful phage therapy for extensive chronic osteoarticular infection in a child resulted in an initial flush of bacterial contents into the bloodstream with an inflammatory response marked by fever, local pain and upregulation of genes associated with autophagy and innate immunity. Pain‐free weight bearing on the affected leg was achieved for the first time since the initial injury, seven weeks after completion of adjunctive phage therapy, and long‐term follow‐up demonstrated radiological improvement.Viable phage was recovered from pre‐dose blood samples up until day 5, consistent with productive infection of the target bacteria throughout the dosing interval.Strong upregulation of several genes linked to the innate immune response coincided with first phage administration, subsequent Pseudomonas DNAemia spike and rise in key inflammatory markers.Hierarchical clustering analysis further confirmed the enrichment of innate immune response‐associated genes on day 2, which appeared to subside over a few days so that by day 29 the gene profile was similar to that of pre‐therapy. [ABSTRACT FROM AUTHOR]

Background: Intense congestion during the Hajj pilgrimage amplifies the risk of meningococcal carriage and disease, and there have been many meningococcal outbreaks reported amongst pilgrims. Thus, a strict vaccination policy is enforced by the host country and either polysaccharide or conjugate quadrivalent meningococcal vaccines are mandatory. However, unlike conjugate vaccines, the polysaccharide vaccine is not thought to reduce pharyngeal carriage of meningococci.Methods: A single-blinded, randomized, controlled trial amongst pilgrims from Saudi Arabia and Australia during the Hajj seasons of 2016-2017 was conducted to compare MenACWY-Conjugate vaccine with MenACWY-Polysaccharide vaccine, to determine if the conjugate vaccine is more effective in reducing asymptomatic carriage of meningococci, and whether the effect may be long-standing. Oropharyngeal swabs were obtained pre-, immediately post- and 6-11 months following completion of Hajj and tested for the presence of meningococci.Results: Amongst 2000 individuals approached, only 1146 participants aged 18-91 (mean 37.6) years agreed to participate and were randomized to receive either the polysaccharide (n = 561) or the conjugate (n = 561) vaccine, 60.8% were male, and 93.5% were from Saudi Arabia. Amongst oropharyngeal swabs obtained before Hajj, only two (0.2%) tested positive for Neisseria meningitidis. Similarly, meningococci were identified in only one sample at each of the post-Hajj and late follow-up visits. None of the carriage isolates were amongst the serogroups covered by the vaccines. A post hoc analysis of the third swabs revealed that 22.4% of all participants (50/223) were positive for Streptococcus pneumoniae nucleic acid.Conclusion: The low overall carriage rate of meningococci found amongst Hajj pilgrims in 2016 and 2017 demonstrates a successful vaccination policy, but neither supports nor refutes the superiority of meningococcal conjugate ACWY vaccine over the polysaccharide vaccine against carriage. Although an association could not be established in this study, molecular epidemiology would help to establish the role of Hajj in facilitating transmission of pneumococci and inform vaccination policy. [ABSTRACT FROM AUTHOR]

I write in response to your article on what it means for a child to have their own room[1] and would like to provide a cross-cultural perspective, since privacy, independence and "personal space" are viewed very differently across different cultures. Co-sleeping and the family bed are the norm in many cultures until children are often into double digit years. Sibling room shares are a necessity but also the expectation, even for those with the economic means to provide "a room of their own" for each child. [Extracted from the article]

The epidemiology of tuberculosis, particularly in children, is highly intertwined with socio-political factors, such as poverty, access to healthcare, and migration. Growing evidence around the world shows that more children have tuberculosis (TB) than was previously thought, most of whom are undiagnosed and untreated, and that TB is a significant cause ofmorbidity andmortality in children inTB endemic areas. Since TB in young children results from recent transmission, the incidence of pediatric TB is a marker of epidemic control in a community and an indirect indicator of the effectiveness of TB control programs. It is estimated that pediatric TB represents between 4 and 21% of all TB cases, depending on the background prevalence in the country, and at least 10 to 20% of the total cases in areas with poor epidemic control. However, a precise estimate of the global burden of TB in children is difficult due to challenges in case ascertainment, diagnosis, and weak surveillance systems inmany countries with a high burden of disease. Several recent estimates highlight these difficulties and provide a starting point to motivate further study. In addition, since drug-resistant TB in young children reflects transmission of resistant strains in the community and occurs with the same frequency as in treatment-naive adults, accurate monitoring of drug-susceptibility patterns in pediatric TB cases will inform optimal empiric treatment regimens in both adults and children, in the context of increasing rates of drug-resistant TB globally. [ABSTRACT FROM AUTHOR]

Aim: The human parechovirus (HPeV) is an increasingly recognised cause of sepsis and central nervous system infection in young infants for which there are limited long-term outcome data. We aimed to assess neurodevelopmental outcome and quality of life in infants following hospitalised HPeV infection.Methods: This cohort study was a 12-month follow-up of infants who were hospitalised with confirmed HPeV infection at the Sydney Children's Hospitals Network during an outbreak in Sydney in 2013. Telephone interviews were conducted with parents/guardians. We administered standardised questionnaires, including: Ages and Stages Questionnaire (ASQ), Liverpool Outcome Score-follow-up, Pediatric Quality of Life Inventory(PedsQL) Infant scales and Short-Form health survey (SF-12).Results: We followed up 46 of 79 infants (58%) aged between 12 and 16 months who had been hospitalised with HPeV infection; 19% showed significant concern in developmental attainment (ASQ3 score <2 standard deviation below population mean), and 50% showed some concern (<1 standard deviation below mean). ASQ3 developmental outcome was associated with the presence of neurodevelopmental sequelae (lower total Liverpool Outcome Score) and poorer health-related quality of life (HRQOL) in physical functioning (PedsQL physical component score), but not overall HRQOL (total PedsQL score) or parental HRQOL (SF-12 scores). No significant associations were identified between clinical or laboratory features during acute hospitalisation and adverse outcome on ASQ3.Conclusions: A high proportion of infants show developmental concern at 12-month follow-up post-hospitalisation with HPeV infection. Clinical features during hospitalisation were not associated with adverse outcomes at 12 months. These results suggest that careful follow-up of young infants hospitalised with HPeV disease may be warranted. [ABSTRACT FROM AUTHOR]

Aim: A prospective observational study was conducted to estimate the prevalence of oropharyngeal carriage of Kingella kingae in healthy Australian pre-school children.Methods: Screening for carriage of K. kingae as well as Streptococcus pyogenes, Streptococcus pneumoniae, Streptococcus agalactiae, Staphylococcus aureus, Haemophilus influenzae, and K. kingae was undertaken using a single bacterial throat swab taken from well children aged 6 months to 4 years. Standard laboratory procedures were used for culture and identification of organisms.Results: One hundred children were enrolled between October and December 2014 at the Children's Hospital at Westmead. Median age was 24.0 months (range 6.1-48.8 months); 52 children were male and 36 attended day-care facilities. Forty-one children had siblings aged less than 5 years and 67 children had siblings of any age. K. kingae oropharyngeal carriage was not detected in any of the children. Rates of carriage of other organisms were: 30% S. aureus, 21% H. influenzae, 2% S. pneumoniae and 2% S. pyogenes. Thirty-eight children were colonised with Kingella denitrificans.Conclusions: Our results suggest that prevalence of K. kingae carriage in pre-school children in Sydney is very low and support local and national guidelines that recommend flucloxacillin as empiric first-line therapy for children with osteoarticular infections. Studies conducted over the winter months and in other Australian centres could help answer outstanding questions regarding differences in carriage rates of K. kingae in children. [ABSTRACT FROM AUTHOR]

Abstract Group B Streptococcus (GBS) is a neonatal pathogen frequently transmitted from maternal asymptomatic vagino-rectal colonization. Co-colonization with multiple GBS serotypes, which has implications for type-specific vaccination strategies, is difficult to detect with standard microbiologic techniques. We designed a nested real-time PCR assay to detect vaginal co-colonization in samples from a cohort of non-pregnant women (N = 433). 6/91 (6.6%) GBS-positive samples harbored ≥2 GBS serotypes, with over-representation of serotype V among co-colonized samples. Serotype IV GBS was more prevalent (>10%) in this cohort than in previously reported United States studies. Ongoing surveillance of GBS serotype epidemiology and co-colonization is indicated. [ABSTRACT FROM AUTHOR]

Meningitecis a CRM197-conjugated meningococcal serogroup C (MenC) vaccine, first licensed in 1999. It has been used as a primary and booster vaccine in infants, toddlers, older children and adults, and has been shown to be immunogenic and well-tolerated in all age groups, including premature infants. Vaccine effectiveness has been demonstrated using combined data on all three licensed MenC conjugate vaccines. Evidence from clinical trials, however, suggests that the different MenC conjugate vaccines behave differently with respect to the induction and persistence of bactericidal antibody and generation of immune memory. It appears thatMeningitechas a less favorable immunologic profile compared particularly to tetanus toxoid (TT) MenC conjugate vaccines. Data from comparative trials have raised interesting questions on priming of the immune system by conjugate vaccines, particularly in infants. The results from these and other studies are reviewed here with specific focus onMeningitec. [ABSTRACT FROM PUBLISHER]

Summary Background The use of different limbs for the administration of sequential doses of an intradermal rabies vaccine was shown to result in reduced vaccine immunogenicity. We aimed to assess whether this phenomenon also occurs with routine infant vaccines. Methods In this open-label, randomised, controlled study, eligible healthy infants 6–12 weeks of age recruited through five clinical trials units (four in the UK and one in Malta) were randomly assigned in a 1:1 ratio to two vaccination groups: consistent limb or alternating limb. Infants in the consistent limb group received the diphtheria–tetanus–acellular pertussis–inactived polio– Haemophilus influenzae type b combined vaccine (DTaP–IPV–Hib) at 2, 3, and 4 months of age, and the pneumococcal conjugate vaccine (PCV13) at 2, 4, and 12 months, all administered to the right leg. Infants in the alternating limb group received DTaP–IPV–Hib in the left leg at 2 months and in the right leg at 3 and 4 months; and PCV13 in the left leg at 2 months, in the right leg at 4 months, and in the left arm at 12 months. All infants in both groups received the combined H influenzae type b and capsular group C Neisseria meningitidis tetanus toxoid conjugate vaccine (Hib–MenC–TT), administered in the left leg at 12 months. Randomisation was achieved by randomly generated codes, with permuted block size of 30, and was stratified by study site. Group allocation was not masked from study staff and parents of participants after enrolment, but group allocation was masked from laboratory staff assessing blood samples. The current study was a prespecified secondary objective of a parent phase 4 trial that assessed the induction of immunity following varying schedules of vaccination with glyco-conjugate capsular group C Neisseria meningitidis (Men C) vaccines in infancy. The objective of the current study was to compare the immunogenicity and reactogenicity of vaccines delivered in either consistent or alternating limbs. Immunogenicity was assessed by comparing serum IgG geometric mean concentrations at 5, 12, 13, and 24 months, analysed per protocol. This study is registered with ClinicalTrials.gov , number NCT01129518 . Findings Between July 5, 2010, and Aug 1, 2013, we enrolled 509 infants and randomly allocated them to the consistent limb group (n=254) or the alternating limb group (n=255). Anti- H influenzae type b anti-polyribosylribitol phosphate IgG geometric mean concentrations were lower in the consistent limb group than in the alternating limb group at 5 months (consistent limb 0·41 μg/mL [95% CI 0·31–0·54] vs alternating limb 0·61 μg/mL [0·45–0·82]; p=0·0268) and at 12 months (0·35 μg/mL [0·28–0·43] vs 0·50 μg/mL [0·40–0·62]; p=0·0136). Anti-tetanus toxoid antibody IgG geometric mean concentrations were lower in the consistent limb group (1·63 IU/mL [95% CI 1·40–1·90]) than in the alternating limb group (2·30 IU/mL [1·97–2·68]) at 13 months (p=0·0008) and at 24 months (0·44 IU/mL [0·37–0·52] vs 0·61 IU/mL [0·51–0·73]; p=0·0074). Anti-pneumococcal IgG geometric mean concentrations were similar between both groups at all timepoints. The proportions of participants who had adverse events did not differ between the two groups. Interpretation Use of different (alternating) limbs for sequential doses of routine infant vaccines does not reduce, and might enhance, immunogenicity. The underlying mechanism for this finding warrants further research. Funding NIHR Oxford Biomedical Research Centre and GlaxoSmithKline Biologicals. [ABSTRACT FROM AUTHOR]

Aim: We measured meningococcal serogroup C (MenC)-specific memory B-cell responses in infants by Enzyme-Linked Immunospot (ELISpot) following different MenC conjugate vaccine schedules to investigate the impact of priming on immune memory. Methods: Infants aged 2 months were randomised to receive 1 or 2 doses of MenC-CRM197 at 3 or 3 and 4 months, 1 dose of MenC-TT at 3 months, or no primary MenC doses. All children received a Haemophilus influenzae type b (Hib)-MenC booster at 12 months. Blood was drawn at 5, 12, 12 months +6 days and 13 months of age. Results: Results were available for 110, 103, 76 and 44 children from each group respectively. Following primary immunisations, and prior to the 12-month booster, there were no significant differences between 1- or 2-dose primed children in the number of MenC memory B-cells detected. One month following the booster, children primed with 1 dose MenC-TT had more memory B-cells than children primed with either 1-dose (p = 0.001) or 2-dose (p<0.0001) MenC-CRM197. There were no differences in MenC memory B-cells detected in children who received 1 or 2 doses of MenC-CRM197 in infancy and un-primed children. Conclusions: MenC-specific memory B-cell production may be more dependent on the type of primary vaccine used than the number of doses administered. Although the mechanistic differences between MenC-CRM197 and MenC-TT priming are unclear, it is possible that structural differences, including the carrier proteins, may underlie differential interactions with B- and T-cell populations, and thus different effects on various memory B-cell subsets. A MenC-TT/Hib-MenC-TT combination for priming/boosting may offer an advantage in inducing more persistent antibody. Trial Registration: EU Clinical Trials Register 2009-016579-31 ClinicalTrials.gov NCT01129518 [ABSTRACT FROM AUTHOR]

Abstract: Background and aims: Serogroup A, C, W-135 and Y meningococcal (MenACWY) conjugate vaccines are recommended for routine adolescent immunisation in the United States and Canada. We evaluated the persistence of bactericidal antibodies through early childhood, following infant immunisation with varying schedules of MenACWY-CRM197 vaccine. Methods: UK and Canadian infants were immunised with 2–3 doses of MenACWY-CRM197 or 2 doses of serogroup C meningococcal (MenC) conjugate vaccine, and either MenACWY-CRM197, 1/5 dose of MenACWY polysaccharide vaccine or no booster at 12 months. Control groups recruited at 60 months had received country-specific infant doses of MenC conjugate vaccine. hSBA titres were measured in participants at 40 and 60 months of age. Results: 382 children were enrolled in 12 groups (22–40 per group). By age 60 months, 3–11% of children primed and boosted with MenACWY-CRM197 had hSBA titres≥1:8 against serogroup A, 14–45% against serogroup C, 57–85% against serogroup W-135 and 42–71% against serogroup Y. Children primed with MenC and boosted with MenACWY-CRM197 had similar results, except for serogroup C (59%). In age-matched controls administered MenC vaccine at 2, 3, and 4 months (UK), 2 and 12 months or 12 months only (Canada), percentages with hSBA titres≥1:8 were 0–3%, 29–53%, 34–36% and 10–29% against serogroups A, C, W-135 and Y respectively. Conclusions: Serogroup-specific bactericidal antibody wane following infant immunisation with MenACWY-CRM197, most markedly against serogroup A. Best persistence against serogroup C is observed with MenC conjugate vaccine priming and MenACWY-CRM197 at 12 months, compared to schedules using only MenACWY-CRM197, with the potential for providing broader protection compared to monovalent MenC vaccines alone. [Copyright &y& Elsevier]

To what extent do children transmit SARS-CoV-2 virus? Concern that children might be major spreaders of SARS-CoV-2, the virus which causes COVID-19, stems largely from past experience: children are certainly major spreaders of other respiratory viral infections, such as influenza and measles. Children infected with SARS-CoV-2 are often asymptomatic: 4-28% in published studies[[1], [3]] and 13% in the most detailed study from China.[1] Asymptomatic child carriers were important spreaders of polio during epidemics, but this does not mean that asymptomatic children often transmit SARS-CoV-2. [Extracted from the article]

Respiratory viruses like coronaviruses and influenza infect us through inhaling droplets or by touching contaminated surfaces then rubbing our nose, mouth or eyes. Effectiveness of N95 respirators versus surgical masks against influenza: A systematic review and meta-analysis. 3 Bartoszko JJ, Farooqi MAM, Alhazzani W, Loeb M. Medical masks vs N95 respirators for preventing COVID-19 in health care workers: A systematic review and meta-analysis of randomized trials. [Extracted from the article]

The article discusses human parechovirus (HPeV) genotype 3 infection in infants and its myocarditis features. It states that due to of its risk of fatal arrhythmias and the opportunity to provide supportive treatment with inotropes such as milrinone, dobutamine and diuretics, its important to detect myocarditis. It mentions that detection of myocarditis include increase in concentration of troponin, electrocardiographic changes and abnormal function on echocardiography.

A 24-day-old boy presented with fever, irritability and poor feeding. Blood culture grew methicillin-resistant Staphylococcus aureus. Cerebrospinal fluid analysis showed pleocytosis, and methicillin-resistant Staphylococcus aureus grew from enrichment broth. Magnetic resonance imaging revealed an epidural abscess extending from C2-3 to T8-9. Staphylococcal infections of the central nervous system are uncommon in neonates. This case demonstrates the importance of performing a lumbar puncture in isolated staphylococcal bacteraemia. The case also highlights that cerebrospinal fluid pleocytosis may indicate a parameningeal focus of infection. [ABSTRACT FROM AUTHOR]