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115 years of malaria data collected in Africa gives the most detailed picture yet of where efforts to control malaria infection are being won and lost across the continent.
Wearable devices for remote monitoring of hospitalized patients with COVID-19 in Vietnam.
Patients with severe COVID-19 disease require monitoring with pulse oximetry as a minimal requirement. In many low- and middle- income countries, this has been challenging due to lack of staff and equipment. Wearable pulse oximeters potentially offer an attractive means to address this need, due to their low cost, battery operability and capacity for remote monitoring. Between July and October 2021, Ho Chi Minh City experienced its first major wave of SARS-CoV-2 infection, leading to an unprecedented demand for monitoring in hospitalized patients. We assess the feasibility of a continuous remote monitoring system for patients with COVID-19 under these circumstances as we implemented 2 different systems using wearable pulse oximeter devices in a stepwise manner across 4 departments.
Tuberculous meningitis: where to from here?
Purpose of reviewTuberculous meningitis (TBM) is associated with significant mortality and morbidity yet is difficult to diagnose and treat. We reviewed original research published in the last 2 years, since 1 January 2018, which we considered to have a major impact in advancing diagnosis, treatment and understanding of the pathophysiology of TBM meningitis in children and adults.Recent findingsStudies have sought to identify a high sensitivity diagnostic test for TBM, with new data on modified Ziehl--Neelsen staining, urinary and cerebrospinal fluid (CSF) lipoarabinomannan and GeneXpert Ultra. Recent studies on CSF biomarkers provide a better understanding of the detrimental inflammatory cascade and neuromarkers of brain damage and suggest potential for novel host-directed therapy. Tryptophan metabolism appears to affect outcome and requires further study. Increased clinical trials activity in TBM focuses on optimizing antituberculosis drug regimens and adjuvant therapy; however, there are few planned paediatric trials.SummaryTuberculous meningitis still kills or disables around half of sufferers. Although some progress has been made, there remains a need for more sensitive diagnostic tests, better drug therapy, improved management of complications and understanding of host-directed therapy if outcomes are to improve.
Tuberculosis treatment in children: The changing landscape.
Traditionally children have been treated for tuberculosis (TB) based on data extrapolated from adults. However, we know that children present unique challenges that deserve special focus. New data on optimal drug selection and dosing are emerging with the inclusion of children in clinical trials and ongoing research on age-related pharmacokinetics and pharmacodynamics. We discuss the changing treatment landscape for drug-susceptible and drug-resistant paediatric tuberculosis in both the most common (intrathoracic) and most severe (central nervous system) forms of disease, and address the current knowledge gaps for improving patient outcomes.
Tuberculous Meningitis in Children: Reducing the Burden of Death and Disability.
Tuberculous meningitis disproportionately affects young children. As the most devastating form of tuberculosis, it is associated with unacceptably high rates of mortality and morbidity even if treated. Challenging to diagnose and treat, tuberculous meningitis commonly causes long-term neurodisability in those who do survive. There remains an urgent need for strengthened surveillance, improved rapid diagnostics technology, optimised anti-tuberculosis drug therapy, investigation of new host-directed therapy, and further research on long-term functional and neurodevelopmental outcomes to allow targeted intervention. This review focuses on the neglected field of paediatric tuberculous meningitis and bridges current clinical gaps with research questions to improve outcomes from this crippling disease.
The role of Kingella kingae in pre-school aged children with bone and joint infections.
ObjectivesThe 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.MethodsInformation 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.ResultsA 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%).ConclusionsThis 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.
Defeating Paediatric Tuberculous Meningitis: Applying the WHO “Defeating Meningitis by 2030: Global Roadmap”
Children affected by tuberculous meningitis (TBM), as well as their families, have needs that lie at the intersections between the tuberculosis and meningitis clinical, research, and policy spheres. There is therefore a substantial risk that these needs are not fully met by either programme. In this narrative review article, we use the World Health Organization (WHO) “Defeating Meningitis by 2030: global roadmap” as a starting point to consider key goals and activities to specifically defeat TBM in children. We apply the five pillars outlined in the roadmap to describe how this approach can be adapted to serve children affected by TBM. The pillars are (i) prevention; (ii) diagnosis and treatment; (iii) surveillance; (iv) support and care for people affected by meningitis; and (v) advocacy and engagement. We conclude by calling for greater integration between meningitis and TB programmes at WHO and at national levels.
Impact of expanding a paediatric OPAT programme with an antimicrobial stewardship intervention.
BackgroundAs treatment out of hospital with outpatient parenteral antimicrobial therapy (OPAT) increases, so too does the risk for patients of being less visible, with potential for suboptimal care.ObjectivesWe aimed to compare pre-expansion and post-expansion (1) successful completion, complications and (2) the impact of an OPAT-specific antimicrobial stewardship (AMS) intervention to mitigate inappropriate antibiotic prescribing.DesignA prospective longitudinal study during two consecutive 12-month periods: period A (1 August 2012 to 31 July 2013) and period B (1 August 2013 to 31 July 2014).SettingThe Hospital-in-the-Home (HITH) programme at The Royal Children's Hospital Melbourne.ParticipantsAll patients who received OPAT during the study period.InterventionsBetween the two periods, the programme expanded from 16 to 32 patients/day. To coincide with this, a combined AMS intervention was introduced: (1) OPAT-specific guidelines and (2) active review of OPAT prescriptions and input by Paediatric Infectious Diseases.Main outcomesSuccessful completion of OPAT, OPAT-related complications, readmission, length of stay and antibiotic appropriateness.ResultsOver 2 years, 646 patients (47% female, median age 7 years) were treated via OPAT for 754 episodes. Patient episodes increased from 254 in period A to 500 in period B, with proportional increases in infants under 1 month and immunocompromised patients. OPAT was successfully completed in 245/251 (98%) versus 473/482 (98%) (OR 1.8, 95% CI 0.7 to 4.5, p=0.3). OPAT-related complications remained low: intravenous catheter-associated complications 16/138 (12%) versus 41/414 (10%), and antibiotic-associated complications 0/254 (0%) versus 2/500 (0.4%). Despite the increase in activity, with the AMS intervention, overall appropriate antibiotic prescribing remained high: 71% versus 76%. Inappropriately long durations reduced from 30/312 (10%) to 37/617 (6%) (OR 0.6, 95% CI 0.4 to 0.99, p=0.04), and median number of days on broad-spectrum antibiotics from 11 (IQR 8-24.5) to 8 (IQR 5-11).ConclusionDuring a period of substantial expansion, we maintained clinical outcomes. A modest AMS intervention reduced some but not all aspects of inappropriate antibiotic prescribing.
Unusual Presentation of Severe Endobronchial Obstruction Caused by Cryptococcus gattii in a Child.
Disease caused by Cryptococcus gattii typically manifests as meningoencephalitis or pulmonary nodules. Endobronchial lesions are rare, and most cases are caused by Cryptococcus neoformans. We describe here a case of endobronchial disease in a child caused by C gattii. The disease spectrum in this patient was notable for the discovery of anti-granulocyte macrophage colony-stimulating factor autoantibodies.
Cryptococcal infections in children: retrospective study and review from Australia.
Aim: Cryptococcosis causes significant morbidity and mortality worldwide, but pediatric data are limited. Methods: A retrospective literature review of Australian pediatric cryptococcosis and additional 10-year audit of cases from a large pediatric network. Results: 22 cases of cryptococcosis in children were identified via literature review: median age was 13.5 years (IQR 7.8-16 years), 18/22 (82%) had meningitis or central nervous system infection. Where outcome was reported, 11/18 (61%) died. Of six audit cases identified from 2008 to 2017, 5 (83%) had C. gattii disease and survived. One child with acute lymphoblastic leukemia and C. neoformans infection died. For survivors, persisting respiratory or neurological sequelae were reported in 4/6 cases (67%). Conclusion: Cryptococcosis is uncommon in Australian children, but is associated with substantial morbidity.
Endobronchial fusariosis in a child following bilateral lung transplant.
We present a case of endobronchial fusariosis following bilateral sequential lung transplantation for idiopathic pulmonary arterial hypertension in a 13 years old boy who was treated successfully with posaconazole and nebulized amphotericin B. We discuss the role of nebulized amphotericin B in treating invasive pulmonary fungal disease in children. To our knowledge, this is the first pediatric case of endobronchial fusariosis reported in the literature.
Multidrug-resistant tuberculosis infection and disease in children: a review of new and repurposed drugs.
The World Health Organization estimates that 10 million new cases of tuberculosis (TB) occurred worldwide in 2017, of which 600,000 were rifampicin or multidrug-resistant (RR/MDR) TB. Modelling estimates suggest that 32,000 new cases of MDR-TB occur in children annually, but only a fraction of these are correctly diagnosed and treated. Accurately diagnosing TB in children, who usually have paucibacillary disease, and implementing effective TB prevention and treatment programmes in resource-limited settings remain major challenges. In light of the underappreciated RR/MDR-TB burden in children, and the lack of paediatric data on newer drugs for TB prevention and treatment, we present an overview of new and repurposed TB drugs, describing the available evidence for safety and efficacy in children to assist clinical care and decision-making.
An Infant with Xpert® Confirmed TB Meningitis in Central Viet Nam.
A 5-month-old boy presented with a focal seizure. Disseminated (miliary) tuberculosis (TB) was diagnosed on chest radiograph and TB meningitis was confirmed using Xpert MTB/RIF®. The case represents the first instance of cerebrospinal fluid Xpert MTB/RIF® testing in children in central Viet Nam. Family screening diagnosed the father with sputum smear-positive TB. The mother and a 2-year-old sibling had no symptoms or signs of TB disease and started preventive therapy. Early TB meningitis diagnosis is the single most important factor influencing clinical outcome, but is difficult due to the non-specific signs and symptoms at disease onset. Late diagnosis is associated with high mortality and severe neurologic handicap, which emphasizes the value of TB preventive therapy in vulnerable young children in close contact with an infectious TB case (recent is generally defined as within the last 12 months).
Vitamin D in newborns. A randomised controlled trial comparing daily and single oral bolus vitamin D in infants.
AimThere are no published data to demonstrate the efficacy of bolus dose vitamin D in newborn infants. The study sought to evaluate this alternative approach of supplementation.MethodsThis single centre, open randomised controlled trial was conducted from August 2013 to May 2014. It compared the efficacy and safety of daily (400 IU) versus a bolus dose (50 000 IU) of cholecalciferol in newborn infants of vitamin D deficient mothers. The primary outcome measure was the rate of 25 hydroxyvitamin D (25OHD) repletion-defined as 25OHD greater than 50 nmol/L. The secondary objective was determining safety using adjusted total serum calcium.ResultsOf 70 eligible infants, 36 received a daily dose and 34 received a single high-dose cholecalciferol. Mean 25OHD in the bolus group (154 nmol/L, 95% confidence interval (CI) 131-177) was higher than the daily group (48 nmol/L, 95% CI 42-54) at 1-2 weeks of age. This was reversed at 3-4 months, (65 nmol/L, 95% CI 59-71) compared with the daily group (81 nmol/L, 95% CI 77-85). More infants in the single bolus group achieved vitamin D repletion (100 vs. 31%) at 1-2 weeks. By 3-4 months, both groups achieved similar vitamin D repletion rates (91 vs. 89%). Mean adjusted total serum calcium in the bolus group were normal at 1-2 weeks (2.73 mmol/L) and 3-4 months (2.55 mmol/L).ConclusionSingle bolus dosing of 50 000 IU cholecalciferol achieves higher 25OHD repletion rates at 1-2 weeks of age compared with daily dosing, but repletion rates were similar by 3-4 months. There was no hypercalcaemia documented with single bolus dosing in this study.