Laporan Pneumonia

[Vira Bhakta]

\r\n\"A polluted environment results in a heavy toll on the health of our children,\" says Dr Maria Neira, WHO Director, Department of Public Health, Environmental and Social Determinants of Health. \"Investing in the removal of environmental risks to health, such as improving water quality or using cleaner fuels, will result in massive health benefits.\"

\r\nFor example, emerging environmental hazards, such as electronic and electrical waste (such as old mobile phones) that is improperly recycled, expose children to toxins which can lead to reduced intelligence, attention deficits, lung damage, and cancer. The generation of electronic and electrical waste is forecasted to increase by 19% between 2014 and 2018, to 50 million metric tonnes by 2018.

\r\nIn households without access to basic services, such as safe water and sanitation, or that are smoky due to the use of unclean fuels, such as coal or dung for cooking and heating, children are at an increased risk of diarrhoea and pneumonia.

\r\nChildren are also exposed to harmful chemicals through food, water, air and products around them. Chemicals, such as fluoride, lead and mercury pesticides, persistent organic pollutants, and others in manufactured goods, eventually find their way into the food chain. And, while leaded petrol has been phased out almost entirely in all countries, lead is still widespread in paints, affecting brain development.

"A polluted environment results in a heavy toll on the health of our children," says Dr Maria Neira, WHO Director, Department of Public Health, Environmental and Social Determinants of Health. "Investing in the removal of environmental risks to health, such as improving water quality or using cleaner fuels, will result in massive health benefits."

For example, emerging environmental hazards, such as electronic and electrical waste (such as old mobile phones) that is improperly recycled, expose children to toxins which can lead to reduced intelligence, attention deficits, lung damage, and cancer. The generation of electronic and electrical waste is forecasted to increase by 19% between 2014 and 2018, to 50 million metric tonnes by 2018.

In households without access to basic services, such as safe water and sanitation, or that are smoky due to the use of unclean fuels, such as coal or dung for cooking and heating, children are at an increased risk of diarrhoea and pneumonia.

Children are also exposed to harmful chemicals through food, water, air and products around them. Chemicals, such as fluoride, lead and mercury pesticides, persistent organic pollutants, and others in manufactured goods, eventually find their way into the food chain. And, while leaded petrol has been phased out almost entirely in all countries, lead is still widespread in paints, affecting brain development.

Data to be presented at IDWeek 2022 showed overall vaccine efficacy against RSV-lower respiratory tract disease (LRTD) in adults aged 60 years and above, with a favourable safety profile

The vaccine was well tolerated with a favourable safety profile. The observed solicited adverse events were typically mild-to-moderate and transient, the most frequent being injection site pain, fatigue, myalgia, and headache.

This phase III efficacy trial is part of a comprehensive RSV evidence-generation programme conducted by GSK. It will continue to evaluate an annual revaccination schedule and longer-term protection over multiple seasons following one dose of the RSV vaccine candidate.

RSV is a common contagious virus affecting the lungs and breathing passages. It is one of the major remaining infectious diseases for which there is currently no vaccine or specific treatment available for adults. Older adults are at high risk for severe disease due to age-related decline in immunity and underlying conditions. RSV can exacerbate conditions, including chronic obstructive pulmonary disease (COPD), asthma and chronic heart failure and can lead to severe outcomes, such as pneumonia, hospitalisation, and death. RSV causes over 420,000 hospitalisations each year and 29,000 deaths in adults in industrialised countries. Adults with underlying conditions are more likely to seek medical advice and have higher hospitalisation rates than adults without these conditions.

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Even though cranial nerves constitute a direct path by which microbes can access the brain, CNS infections are relatively rare, and only a small number of infectious agents are thought capable of accessing the brain via these paths. The nerves are well-protected physically and immunologically by the nasal epithelium which exhibits powerful innate and adaptive immune system components. Together with the associated nasopharynx-associated lymphoid tissue (NALT), the epithelium constitutes the first defence against microbes25. Injuries to the nasal epithelium are, however, relatively common26 and may expose the underlying cranial nerves to infection. Experimental injuries to the nasal epithelium of mice has been shown to increase the risk of bacterial invasion of the olfactory nerve and bulb by some bacteria27,28. Most microbes are, however, likely eliminated by phagocytic glia, olfactory ensheathing cells (OECs) and trigeminal Schwann cells (TgSCs), should they penetrate the epithelium and reach the nerves29,30,31. The glia limitans layer between the peripheral nerves and brain, populated by astrocytes, constitutes a further immunological barrier against CNS infection32,33. Whilst it is largely unknown why certain infectious agents can infect the CNS via cranial nerves, one key mechanism is thought to be the ability of these pathogens to infect and survive in OECs, TgSCs and astrocytes, as well as in microglia (the main phagocytes inside CNS tissue)20,27,28,34,35.

Chlamydiae are obligate intracellular bacteria with a unique biphasic life-cycle reviewed in36. Outside of host cells, Chlamydiae exist as infectious, biologically inactive elementary bodies (EBs), which exhibit strong resistance to environmental stress. C. pneumoniae EBs can become internalized into host cells, including many phagocytes1,37,38. The EBs are resistant to endosomal/lysosomal degradation, and inside the host cell transform into reticulate bodies (RBs). RBs replicate in inclusions (modified cellular vacuoles), which expand in size as the bacteria replicate. After approximately 72 h (in cell culture), the RBs transform into EBs, which are released by cell lysis and can infect new cells (exit via extrusion of membrane-bound compartments can also occur39). Chlamydiae can also persistently infect cells40 which is likely relevant for the link to chronic diseases1. Persistent Chlamydia infection can last for many years, and the persistent Chlamydia bacteria can re-activate41,42.

Heads and tissues including the olfactory mucosa (containing the olfactory nerve fascicles), olfactory bulb, trigeminal nerve and the brain (the remainder of the brain after removal of olfactory bulbs) were collected from euthanized mice, 1, 3, 7 days and 28 days post inoculation, for bacterial load determination and histology.

Chlamydia pneumoniae IFUs were detected by direct inoculation of tissue homogenate onto HEp-2 cells which were seeded on 96-well plates with 4000 cells/well. After 72 h, the C. pneumoniae inclusions in the entire wells were visualized by confocal microscopy and the numbers of IFUs isolated from the homogenates (IFU/mL) were determined (see workflow in Fig. 1).

Schematics illustrating the process for quantifying the amount of viable infectious C. pneumoniae present in various mouse tissues. (A) Mice were first intranasally inoculated with C. pneumoniae (i), some with epithelial injury and some without. Following either 24 h, 3 days or 7 days or 28 days post inoculation, selected tissues were collected and homogenised in tubes (ii). Homogenates were serially diluted onto HEp-2 cells and incubated (iii). Cells were fixed and immunolabelled for C. pneumoniae inclusions, which were counted and the number of inclusion-forming units (IFUs) per mL of homogenate was determined. Data were then compiled into organ (tissue) load graphs (see Fig. 2). (B) Microscopic image showing a sagittal tissue section of a mouse brain. Cell nuclei/DNA are shown in blue (DAPI stain). Key anatomical locations include the nasal cavity (NC), olfactory epithelium (OE), olfactory bulb (OB), trigeminal nerve (Tg; not visible so approximate location is shown by white dotted line) and the brain. Scale bar in m.

The experimental procedures used in the study were conducted with the approval of the Griffith University Biosafety Committee (NLRD/09/15_var7) and the Griffith University Animal Ethics Committee (MSC/08/18/AEC) in accordance with guidelines of the Australian Commonwealth Office of Gene Technology Regulator and the National Health and Medical Research Council of Australia. All the animal experiments in this study are reported in accordance with ARRIVE guidelines ( ).

Despite being able to isolate viable C. pneumoniae from the brain (beyond the bulb), we did not find definitive C. pneumoniae inclusions in brain tissue sections from these mice (not shown), suggesting that inclusions in brain tissue were too small or sparse to be confirmed by histology when screening tissue sections.

Mice were then sacrificed 3 and 7 days after inoculation, followed by determination of the amounts of viable C. pneumoniae (IFUs) in tissues (Fig. 2A,B), as well as immunohistochemistry of tissue sections (Fig. 4). Whilst described separately here for better clarity, these experiments were conducted simultaneously to the experiment groups described for Fig. 2 (so that methimazole-induced epithelial injury followed by C. pneumoniae inoculation could be compared to C. pneumoniae inoculation alone).

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