Burden of respiratory tract infections at post mortem in Zambian children

Background: Autopsy studies are the gold standard for determining cause-of-death and can inform on improved diagnostic strategies and algorithms to improve patient care. We conducted a cross-sectional observational autopsy study to describe the burden of respiratory tract infections in inpatient children who died at the University Teaching Hospital in Lusaka, Zambia. Methods: Gross pathology was recorded and lung tissue was analysed by histopathology and molecular diagnostics. Recruitment bias was estimated by comparing recruited and non-recruited cases. Results: Of 121 children autopsied, 64 % were male, median age was 19 months (IQR, 12-45 months). HIV status was available for 97 children, of whom 34 % were HIV infected. Lung pathology was observed in 92 % of cases. Bacterial bronchopneumonia was the most common pathology (50 %) undiagnosed ante-mortem in 69 % of cases. Other pathologies included interstitial pneumonitis (17 %), tuberculosis (TB; 8 %), cytomegalovirus pneumonia (7 %) and pneumocystis Jirovecii pneumonia (5 %). Comorbidity between lung pathology and other communicable and non-communicable diseases was observed in 80 % of cases. Lung tissue from 70 % of TB cases was positive for Mycobacterium tuberculosis by molecular diagnostic tests. A total of 80 % of TB cases were comorbid with malnutrition and only 10 % of TB cases were on anti-TB therapy when they died. Conclusions: More proactive testing for bacterial pneumonia and TB in paediatric inpatient settings is needed

Framework for Improving Governance and Quality of Rural Oncology Outreach Services

PURPOSE: Rural outreach is a common method for delivering oncology services closer to rural residents; however, there is no clear service framework for supporting its quality and governance. This work aimed to develop an agreed framework for improving the governance and quality of a rural oncology outreach service. METHODS: A Six Sigma and participatory action approach was used. Key clinicians and managers identified project goals and scope, participated in several rounds of interviews and medical record audits, and discussed findings to reach consensus about a framework for quality outreach service delivery from one regional cancer center supporting two rural hospital sites (5-chair nurse-led oncology units). RESULTS: Themes included strong investment by stakeholders in maintaining the outreach service for its importance for rural populations. The referral, treatment, and clinical governance processes were implicitly understood between stakeholders but not well documented. Medical record audits of treated patients identified important gaps in clinical information at rural sites. Through reflection and discussion, consensus was reached about a framework for quality service delivery. The participatory action planning cycle involving sites in regular discussions fostered information sharing, strong engagement, and uptake of the final framework. CONCLUSION: The framework was applied to a memorandum of understanding for planning, governance, and outcomes monitoring and provides a basis for developing new and benchmarking existing oncology outreach services

Effects of <i>Klebsiella pneumoniae</i> Bacteriophages on IRAK3 Knockdown/Knockout THP-1 Monocyte Cell Lines

Bacterial sepsis characterised by an immunosuppressive and cytokine storm state is a challenge to treat clinically. While conventional antibiotics have been associated with exacerbating the cytokine storm, the role that bacteriophages may play in immune modulation of sepsis remains unclear. Bacteriophages are bacterial viruses that have the capacity to lyse specific bacteria and hence provide a natural alternative to antibiotics. K. pneumoniae is known to cause sepsis in humans, and in this study we isolated two lytic bacteriophages against this pathogen, one of which was a novel jumbo bacteriophage. We employed THP-1 monocyte cell lines, with different functional phenotypes for the interleukin-1 receptor associated kinase 3 (IRAK3- a cytoplasmic homeostatic mediator and prognostic marker of inflammation), to evaluate the role of the K. pneumoniae bacteriophages in modulating the immune response in-vitro. We showed for the first time that bacteriophages did not stimulate excessive production of tumour necrosis factor alpha, or interleukin-6, in THP-1 monocyte cell lines which displayed varying levels of IRAK3 expression

A Novel Approach to Managing a COVID-19 Outbreak at a Farm in Outer Regional Victoria, Australia

The coronavirus disease (COVID-19) has been established as a major occupational health and safety issue that compounds pre-existing socioeconomic inequalities such as access to basic health services. This is exacerbated in migrant farmworkers who are an essential workforce in maintaining food supply across the country. An outbreak occurred in a remote part of Victoria with limited access to healthcare resources. Existing relationships allowed the Loddon Mallee Public Health Unit to quickly engage farm management and local pathology services and provide cultural and language support. After contact-tracing and comprehensive clinical review, rather than isolate positive cases, those who were asymptomatic and willing to work continued to do so whilst negative workers were in quarantine. Outbreak management and public health actions were quickly implemented even when the nationwide state-testing and contact-tracing systems were experiencing significant strain due to the rapid escalation in case numbers. Despite a large outbreak (68/74 workers), the management of the outbreak allowed asymptomatic cases to perform their work so farm productivity remained uninterrupted. Cases&rsquo; health status was closely monitored, with no adverse outcomes in a high-risk population. COVID-19 negative workers safely quarantined away from positive cases until the closure of the outbreak

Characterization of Novel Lytic Bacteriophages of Achromobacter marplantensis Isolated from a Pneumonia Patient

Achromobacter spp. are becoming increasingly associated with lung infections in patients suffering from cystic fibrosis (CF). A. marplatensis, which is closely related to A. xylosoxidans, has been isolated from the lungs of CF patients and other human infections. This article describes the isolation, morphology and characterization of two lytic bacteriophages specific for an A. marplatensis strain isolated from a pneumonia patient. This host strain was the causal agent of hospital acquired pneumonia&ndash;the first clinical report of such an occurrence. Full genome sequencing revealed bacteriophage genomes ranging in size from 45901 to 46,328 bp. Transmission electron microscopy revealed that the two bacteriophages AMA1 and AMA2 belonged to the Siphoviridae family. Host range analysis showed that their host range did not extend to A. xylosoxidans. The possibility exists for future testing of such bacteriophages in the control of Achromobacter infections such as those seen in CF and other infections of the lungs. The incidence of antibiotic resistance in this genus highlights the importance of seeking adjuncts and alternatives in CF and other lung infections

Children infected by human herpesvirus 6B with febrile seizures are more likely to develop febrile status epilepticus: A case-control study in a referral hospital in Zambia

BACKGROUND Human herpesvirus 6B (HHV-6B) is the causative agent of Roseola infantum, and has also been suggested to play a role in the pathogenesis of febrile seizures in young children, a percentage of whom go on to develop febrile status epilepticus (FSE), but the existing data is conflicting and inconclusive. HHV-6A is a distinct species, rarely detected in most parts of the world, but prior studies suggest a higher prevalence in febrile African children. We describe a case-control study comparing the frequency of HHV-6A and/or HHV-6B infections in children with febrile seizures (including FSE) and a control group of febrile children without seizures. METHODS We recruited children aged 6 to 60 months admitted with a febrile illness with (cases) or without (controls) seizures presenting within 48 hours of commencement of fever. Three milliliters of whole blood was centrifuged and plasma stored at -80°C for pooled screening for HHV-6B and HHV-6A by Taqman real-time polymerase chain reaction. RESULTS 102 cases and 95 controls were recruited. The prevalence of HHV-6B DNA detection did not differ significantly between cases (5.8% (6/102)) and controls (10.5% (10/95)) but HHV-6B infection was associated with FSE (OR, 15; 95% CI, [1.99-120]; P= 0.009). HHV-6A was not detected. CONCLUSION Prevalence of HHV-6B was similar among cases and controls. Within the FS group, HHV-6B infection was associated with FSE, suggesting HHV-6B infections could play a role in the pathogenesis of FSE

High rates of congenital cytomegalovirus infection linked with maternal HIV infection among neonatal admissions at a large referral center in sub-Saharan Africa.

BACKGROUND:  Congenital cytomegalovirus (CMV) infection is the major infectious cause of birth defects and hearing loss globally. There is a growing recognition of the potential clinical impact of congenital CMV infections in high-seroprevalence settings. METHODS:  A cross-sectional study of neonatal admissions at a large referral center in sub-Saharan Africa to determine the prevalence of both symptomatic and asymptomatic congenital CMV infection was performed. Real-time polymerase chain reaction was used to screen DNA-extracted sera, urine, and saliva, and an enzyme-linked immunosorbent assay was used to screen serum samples for anti-CMV immunoglobulin M. Multivariate binary logistic regression was used to identify risk factors associated with increased odds of congenital CMV infection. RESULTS:  Congenital CMV was detected in 3.8% (15/395) of neonates. Among these infants, 6 of 15 (40%) presented with jaundice, 1 of whom also had petechiae. Congenital CMV infection was detected in 9 of 79 (11.4%; 95% confidence interval [CI], 6.1%-20.3%) neonates born to human immunodeficiency virus (HIV)-infected mothers, and both maternal HIV (odds ratio [OR], 6.661 [95% CI, 2.126-20.876], P = .001) and jaundice (OR, 5.701 [95% CI, 1.776-18.306], P = .003) were independently linked with significantly increased odds of congenital CMV infection. CONCLUSIONS:  Congenital and early infant CMV infections may have important consequences for child health in sub-Saharan Africa and other high HIV and CMV seroprevalence populations globally