The 2019 novel coronavirus (2019-nCoV) causes novel coronavirus pneumonia (NCP). Given that approved drug repurposing becomes a common strategy to quickly find antiviral treatments, a collection of FDA-approved drugs can be powerful resources for new anti-NCP indication discoveries. In addition to synthetic compounds, Chinese Patent Drugs (CPD), also play a key role in the treatment of virus related infections diseases in China. Here we compiled major components from 38 CPDs that are commonly used in the respiratory diseases and docked them against two drug targets, ACE2 receptor and viral main protease. According to our docking screening, 10 antiviral components, including hesperidin, saikosaponin A, rutin, corosolic acid, verbascoside, baicalin, glycyrrhizin, mulberroside A, cynaroside, and bilirubin, can directly bind to both host cell target ACE2 receptor and viral target main protease. In combination of the docking results, the natural abundance of the substances, and botanical knowledge, we proposed that artemisinin, rutin, glycyrrhizin, cholic acid, hyodeoxycholic acid, puerarin, oleanic acid, andrographolide, matrine, codeine, morphine, chlorogenic acid, and baicalin (or Yinhuang Injection containing chlorogenic acid and baicalin) might be of value for clinical trials during a 2019-nCov outbreak.

Malaria is one of the life-threatening disease caused by the Anopheles mosquitoes affecting the human red blood cells. It is the global health concern which is quite common in tropical as well as sub-tropical parts of the World. Therefore, it is an important to have an effective computer aided system in place for early detection and treatment. State of the art machine learning techniques are used to detect the infected malaria cells from the pool of images. As the visual heterogeneity of the malaria dataset is highly complex and dynamic, therefore higher number of images are needed to train the machine learning models effectively. However, hospitals as well as medical institutions do not share the medical image data for collaboration due to general data protection regulation (GDPR) and data protection act (DPA). To overcome this collaborative challenge, our research is inspired to use the real-time medical image data while using the framework of federated learning (FL) framework that will ensure the data privacy while mutual collaboration of hospitals and medical institutes. We have used the state of the art machine learning models that include the Resnet50 and densenet in a federated learning framework. We have experimented both models in different settings and our preliminary results showed that the densenet model performed better in accuracy (75%) in contrast to resnet50 (72%) while considering 8 clients, while the trend is observed common in 4 clients with the similar accuracy of 94% and 6 client showed that the densenet model performed quite well with the accuracy of 92% while resnet50 achieving only 72%.

The discovery of interesting inter-relationships between the different malaria epidemiological parameters is essential towards the disease control. However, existing associative rule-based machine learning algorithms for pattern discovery are slow while working on high-dimensional Malaria Indicator Survey (MIS) data, with the further challenge of data under fitting and inadequate result visualization. Hence, this work proposed a novel and efficient associative rule-based machine-learning algorithm with enhanced graphical visualization capacity for rigorous and confident biological result interpretation for malaria control. Through empirical and asymptotic comparative time-complexity performance evaluations, the proposed algorithm scaled better than other existing associative rule-based machine learning algorithms while maintaining its accuracy. The algorithm was applied to two real MIS data sets obtained from the Demographic and Health Survey repository and other supplementary literature source using Nigeria as a case study. The resulting interesting malaria epidemiological discovered novel trends were: a) the malaria disease might not be associated with the anemia symptom; b) there was no significant association between the anemia symptom and the wealth indices of individuals; c) there were other parameters associated with the insecticide resistance capacity of the malaria vector asides the knock down resistance alleles; d) the population dynamics of the malaria vector was not associated with the malaria disease endemicity. In conclusion, this work developed a computationally efficient and user-friendly associative rule-based machine-learning algorithm called E_Apriori for the control of the malaria disease.

Plasmodium vivax causes the second highest number of malaria morbidity and mortality cases in humans. Several biological traits of this parasite species, including the formation of dormant stages (hypnozoites) that persist inside the liver for prolonged periods of time, present an obstacle for intervention measures and create a barrier for the elimination of malaria. Research into the biology of hypnozoites requires efficient systems for parasite transmission, liver stage cultivation and genetic modification. However, P. vivax research is hampered by the lack of an in vitro blood stage culture system, rendering it reliant on in vivo derived, mainly patient material, for transmission and liver stage culture. This has also resulted in a limited capability for genetic modification, creating a bottleneck in investigations into the mechanisms underlying the persistence of the parasite inside the liver. This bottleneck can be overcome through optimal use of the closely related and experimentally more amenable nonhuman primate (NHP) parasite Plasmodium cynomolgi as model system. In this review we discuss the genetic modification tools and liver stage cultivation platforms available for studying P. vivax persistent stages and highlight how their combined use may advance our understanding of hypnozoite biology.

Malaria remains a primary public health challenge in Africa, and there is growing interest in leveraging artificial intelligence (AI) to raise malaria interventions. This research examines the possible influence, challenges, and recommendations for implementing AI-based personalized malaria interventions in Africa. AI offers several opportunities in malaria management, including early detection and prediction of outbreaks, improved diagnosis, personalized interventions, optimal treatment recommendations, surveillance and response, resource optimization, and research innovation. However, the implementation of AI in malaria interventions faces various challenges. These include data availability and quality, infrastructure and resource constraints, contextual relevance and generalizability, ethical and privacy considerations, integration into healthcare workflows, and the need to build trust and acceptance among stakeholders. To address these challenges, it is recommended to strengthen data infrastructure, build local capacity in AI technologies, contextualize AI models to local settings, address ethical considerations, establish monitoring and evaluation frameworks, promote collaboration and knowledge sharing, and secure sustainable funding and long-term commitment. By considering these recommendations, stakeholders can work towards implementing AI-based personalized malaria interventions in Africa that can contribute to improving malaria control outcomes, reducing the weight of the disease, and advancing public health in the region.

Background/Purpose: Over the last two decades, malaria has remained a major worldwide public health concern, especially in the developing countries leading to high morbidity and mortality among children. Nigeria is the world most burdened malaria endemic nation, contributing more than a quarter of global malaria cases. This study determined the prevalence of malaria among children 6-59 months in Nigeria, and the effects of individual and contextual factors. Methods: The study utilized data from 2018 Nigeria Demographic and Health Survey (NDHS) involving a weighted sample size of 10,185 children who were tested for malaria using rapid diagnostic test (RDT). Given the hierarchical structure of the data set, such that children at level-1 are nested in community at level-2, and nested in states and Federal Capital Territory (FCT) at level-3, multilevel mixed effect logistic regression models were used for the analysis. Results: The proportion of children 6-59 months of age in Nigeria that had malaria fever positive as assessed by RDTs was 35.5% (3,418/10185), (CI: 33.9-37.1). Kebbi State had the highest proportion of children 6-59 months who were malaria positive, 77.6%, (CI: 70.2-83.5), followed by Katsina State, 55.5%, (CI: 47.7-63.1). The Federal Capital Territory (FCT), Abuja had the proportion of 29.6%, (CI: 21.6-39.0), malaria positive children of 6-59 months of age. Children between the age of 48 and 59 months were 2.68 times more likely to have malaria fever than children 6-11 months of age (AOR=2.68, 95% CI: 2.03-3.54). Also, children from the rural area (AOR= 2.12, 95% CI: 1.75-2.57), were more likely to suffer from malaria infection compare with children from urban area. Conclusion: The study identified some individual and contextual predictors of malaria among children in Nigeria. These factors are areas that need to be considered for policy designs and implementations toward control and total elimination of malaria-related morbidity and mortality among children in Nigeria.

Severe malaria in adults is not well studied in Sahelian Africa. Clinical features and mortality associated with severe Plasmodium falciparum malaria in adult patients hospitalized in Kiffa, southern Mauritania, were analysed. Patients over 15 years old admitted for severe malaria between August 2016 and December 2019 were included in the present retrospective study. The World Health Organization (WHO) criteria were used to define severe malaria. The presenting clinical characteristics and outcome were compared. Of 4266 patients hospitalized during the study period, 573 (13.4%) had a positive rapid diagnostic test for malaria, and 99 (17.3%; mean age, 37.5 years; range 15–79 years; sex-ratio M/F, 2.1) satisfied the criteria for severe malaria. On admission, the following signs and symptoms were observed in more than one-fourth of the patients: fever (98%), impairment of consciousness (81.8%), multiple convulsions (70.7%), cardiovascular collapse (61.6%), respiratory distress (43.4%), severe anaemia ≤ 80 g/L (36.4%), haemoglobinuria (27.3%), and renal failure (25.3%). Patients were treated with parenteral quinine or artemether. Fourteen (14.1%) patients died. Multiple convulsions, respiratory distress, severe anaemia, haemoglobinuria, acute renal failure, jaundice, and abnormal bleeding occurred more frequently (P < 0.05) in deceased patients. Mortality due to severe falciparum malaria is high among adults in southern Mauritania. An adoption of the WHO-recommended first-line treatment for severe malaria, i.e. parenteral artesunate, is required to lower the mortality rate associated with severe malaria.

In the aftermath of the COVID pandemic, post-COVID-19 syndrome (PCS) remains a challenge and may continue to represent a major health problem in the future. Moreover, the influence of type 2 diabetes and being overweight on PCS remains unclear. This study aimed to assess this influence. We performed an observational study from October 2020 to July 2022, which included 466 patients (269 males and 197 females) with a median age of 65. They were hospitalized due to COVID-19 pneumonia and had persistent symptoms after 1 month of COVID-19 infection. The patients were divided into four groups according to the study objectives: patients with type 2 diabetes, overweight patients, overweight patients with type 2 diabetes, and normal-weight patients without type 2 diabetes. The clinical and demographic data collected during hospitalization and regular visits at the Community Healthcare Center dr. Adolf Drolc Maribor were analyzed. Our results showed that type 2 diabetes patients had a more difficult course of treatment and longer hospitalization. Moreover, more type 2 diabetes patients underwent rehabilitation than the other study groups. The prevailing symptoms in our patients with PCS were dyspnea and fatigue, mostly in female patients with type 2 diabetes. Our study also showed that more women with type 2 diabetes and more overweight women with type 2 diabetes suffered from secondary infections. Further, more overweight patients were treated in the intensive care unit compared to the other groups. However, our study showed an interesting result that patients with type 2 diabetes had the shortest PCS durations. Type 2 diabetes and being overweight are risk factors for PCS onset and prolonged duration. Therefore, our data that revealed a shorter duration of PCS in type 2 diabetes patients compared to the other investigated groups was unexpected. We believe that answering this question regarding the results will enable us to improve PCS treatment in general.

Objective: To evaluate the effect of rectal Ozone (O3) in severe COVID-19 pneumonia in two different cohorts differing in location (Madrid vs Zilina), ethnicity (Slovakian vs Spanish cohorts) and age. Material and Methods: In a multicenter-study, 32 severe bilateral-COVID-19-pneumonia patients and (+) RT-PCR (reverse transcriptase polymerase chain reaction) SARS-CoV-2 were evaluated (16 from each cohort). Primary outcomes: a) clinical (O2-saturation); b) biochemical (Lymphocyte-count, Fibrinogen, D-Dimer, Urea, Ferritin, LDH [lactate dehydrigenase], IL-6 and CRP [c-reactive protein]); and c) radiological improvement. Secondary outcomes: a) days-of-hospitalization, b) mortality-rate before discharge. The Ozone-protocol consisted of 10 sessions of intra-rectal Ozone, total dose 5.25 mg (150 mL volume, 35 g/ml concentration). The Standard-of-care protocol included O2 supply, antivirals (Remdesivir / Isoprinosine), corticosteroids (Dexamethasone / Metilprednisolone), monoclonal antibodies (Anakinra / Tocilizumab), antibiotics (Azytromicine), anticoagulants (Enoxaparine / Fraxiparine). Protocol was approved by Health Care Ethics Committee (Report 15/4/2020) of our Hospital and by Ethics Committee for Medical Investigation of La Princesa’s Hospital (ACTA CEIm 12/20, 28/5/20, Registry 4146). Results: Patients in Slovakian cohort were younger (53.38 vs 84.69 years). Grade of severity was worse in Spanish-cohort (4.78 vs 3.30 points). Length of stay was superior in Spanish-cohort (27.38 vs 10.07 days). Both cohorts improved O2-saturation and Lymphocyte-count. Inflammation biomarkers (Fibrinogen, D-Dimer, Urea, Ferritin, LDH, CRP and IL-6) decreased in both cohorts. In Spanish-cohort, Urea and Ferritin improvement was not significant (p>0.05), while in Slovakian-cohort, Urea, Fibrinogen and LDH were not significant (p>0.05) Radiological signs of bilateral pneumonitis decreased on both cohorts. Mortality was similar (12.5%). Conclusion: After Standard of care protocol, Rectal Ozone improved O2-saturation, decreased inflammation biomarkers and improved Taylor’s radiological scale in both cohorts. Although age, grade of severity and days of hospitalization were inferior in Slovakian cohort, mortality was similar in both cohorts, but inferior if compared to an external control cohort.

Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by a broad array of clinical signs. In this study, we aimed to use intravenous immunoglobulins (IVIG), called intacglobin, as a monotherapy to manage SLE in three patients. Laboratory investigations for SLE diagnosis were performed, including the detection of anti-nuclear antibodies (ANA) and SLE confirmation by detecting high titers of anti-dsDNA antibodies. C3 and C4 serum levels were assessed, as well as the determination of immunoglobulins. The SLEDAI score was measured to determine whether a significant degree of disease activity existed and as a prognostic value. The evaluation of any chest infection was performed by chest-X-ray. The patients were treated with five–ten g/day of IVIG for six consecutive days, followed by five–ten g/month. Immunological evaluation demonstrated that patients presented with a flare of SLE with high titers of ANA and anti-dsDNA antibodies, low C3 and C4, and elevated immunoglobulin levels. The SLEDAI score falls from 10 to below 3, and chest infections in some patients are cleared up. The postulated mechanisms of action of IVIG demonstrated that it could be used as an immunosuppressor, immunomodulator, and antimicrobial agent in patients with SLE.

Therapeutic options for the highly pathogenic human Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) causing the current pandemic Coronavirus disease (COVID-19) are urgently needed. COVID-19 is associated with viral pneumonia and acute respiratory distress syndrome causing significant morbidity and mortality. The proposed treatments for COVID-19, such as hydroxychloroquine, remdesivir and lopinavir/ritonavir, have shown little or no effect in the clinic. Additionally, bacterial and fungal pathogens contribute to the SARS-CoV-2 mediated pneumonia disease complex. The antibiotic resistance in pneumonia treatment is increasing at an alarming rate. Therefore, carbon-based nanomaterials (CBNs), such as fullerene, carbon dots, graphene, and their derivatives constitute a promising alternative due to their wide-spectrum antimicrobial activity, biocompatibility, biodegradability and capacity to induce tissue regeneration. Furthermore, the antimicrobial mode of action is mainly physical (e.g. membrane distortion), which is characterized by a low risk of antimicrobial resistance. In this review, we evaluated the literature on the antiviral activity and broad-spectrum antimicrobial properties of CBNs. CBNs had antiviral activity against 12 enveloped positive-sense single-stranded RNA viruses similar to SARS-CoV-2. CBNs with low or no toxicity to the humans are promising therapeutics against COVID-19 pneumonia complex with other viruses, bacteria and fungi, including those that are multidrug-resistant.

The short study implicates few basic similarities of COVID-19 such as diseases origination, symptoms, diagnosis with other relatable viral diseases viz SARS-CoV, common Flu, pneumonia etc. In the present situation, other viral diseases are frequently chaotic and misled with COVID-19 disease because of few clinical features similarities in signs and symptoms and also due to lack of specific diagnostic test. To avoid unnecessary suspects, quarantines of false positive results and to prevent the spread of COVID-19 diseases, the scientific technical research field are highly encourage to implement an efficient, rapid and sophisticated superior test for early stages of infection detection. It will be significantly convenient for physician, laboratory technicians and most importantly the common population facing a psychological disturbance.

Different products from a unique Propolis extract, Propolis (bee glue), an of resinous consistency produced by bees, has been used as indigenous medicine for the treatment of several diseases in some contrary. Safety assessment of propoils extracts with respect to antimicrobial activity against three bacterial isolates, Proteus Mirabilis , Klebsiella Pneumonia and Staphylococcus Qureus.The result showed that the main composition of the extract was Anthraquinone, the last one was responsible for the biological activity of the extract. FT-IR, UV results showed more than eight peaks for represent the main fine composition of the extract. The present study also showed that the extract has antibacterial activity against three bacterial isolates

Currently, there is no effective antiviral therapy recommended for the new coronavirus disease 2019 pneumonia (COVID-19). The purpose of this pilot study was to evaluate the safety of Ozonized Saline Solution (O₃SS) used as a complementary therapy in adult patients COVID-19. Twenty-five adult patients who were hospitalized with mild to severe COVID-19 symptoms, who met the inclusion criteria and were being treated from April 18^rd to April 26th, 2020, at the Viamed Virgen De La Paloma Hospital, Madrid, Spain were included in this study. Patients were allocated to receive standard care (SC) that included 200-400 mg hydroxychloroquine twice daily for 5-7 days plus Tocilizumab 400 mg twice daily for 5 days, low molecular weight heparin (LMWH) and 40 mg-60 mg metil-prednisone plus O₃SS, 200 mL, 3-5 µg/mL daily for 10 days. No control group was included, data were compared to clinical trials in this subject. Primary outcomes of treatment with O₃SS were an improvement of clinical symptoms and a reduction in mortality. Secondary end points evaluated included participant clinical status, laboratory examinations, and duration of viral shedding. None of the patients treated with SC + O₃SS died. Improvements in symptoms such as dyspnea, weakness, and reduction in body temperature were observed and corresponded with an improvement of laboratory finding including D-dimer, fibrinogen, LDH, and CRP. No side effects from the O₃SS treatment were observed. Conclusions: COVID-19 patients with mild to severe symptoms who received intravenous O₃SS as a complementary therapy demonstrated no side effects. This preliminary data will be served as base for a future study of the efficacy of this therapy.

Background Critical patients with novel coronavirus pneumonia ( COVID-19) have worse outcome and high mortality. However, the histopathology of critical patient with COVID-19 remains undisclosed. Methods We performed the whole lung biopsy, and described the pathological changes of critical COVID-19 patient done with transplant by HE staining, immunohistochemistry and special staining observed under the microscopy. Findings The whole lungs displayed diffuse congestive appearance and partly haemorrhagic necrosis on gross examination. The haemorrhagic necrosis was prominently present in outer edge of the right lower lung. The cut surfaces of the lung displayed severe congestive and haemorrhagic changes. The main pathological changes showed massive pulmonary interstitial fibrosis, and partly hyaline degeneration, variable degrees of hemorrhagic pulmonary infarction. Small vessels hyperplasia, vessel wall thickening, lumen stenosis, occlusion and microthrombosis formation. Focal monocytes, lymphocytes and plasma cells infiltrating into pulmonary interstitium. Bronchiolitis and alveolitis with proliferation, atrophy, desquamation and squamous metaplasia of epithelial cells. Atrophy, vacuolar degeneration, proliferation, desquamation and squamous metaplasia in alveolar epithelial cells. Alveolar cavity congestion was prominent, and contained mucus, edema fluid, desquamated epithelial cells, and inflammatory cells. We also found several multinucleate giant cells and intracytoplasmic viral inclusion bodies. Special stains including Masson stain, sirius red staining, reticular fibers staining indicated massive pulmonary interstitial fibrosis. Immunohistochemistry showed positive for immunity cells including CD3, CD4, CD8, CD20, CD79a, CD5, CD38 and CD68. Interpretation We demonstrate the pathological findings of critical patient with COVID-19, which might provide a deep insight of the pathogenesis and severity of this disease.

Antibiotics’ effect on Mycoplasma pneumoniae (MP) infection still remains controversial. A prospective study of 257 children with MP pneumonia during a recent epidemic (2015-2016) was conducted. All MP pneumonia patients were treated with corticosteroids within 24-36 h after admission. Initially, oral prednisolone (1 mg/kg) or intravenous methylprednisolone (IVMP) (1-2 mg/kg) was administered for mild pneumonia patients, and IVMP (5 -10 mg/kg/day) for severe pneumonia patients. If patients showed persistent fever for 36-48 hours or disease progression, additive IVMP (5 mg/kg or 10 mg/kg) was given. Eighty-five patients received only a broad-spectrum antibiotic without macrolide. The mean age and the male:female ratio were 5.6 ± 3.1 years, respectively. Seventy-four percent of patients (190/257) showed immediate defervescence within 24 h, and 95.7% (246/257) of patients showed defervescence within 72 h with improvements in clinical symptoms. Eight patients who received additive IVMP also showed clinical improvement within 48 h without adverse reactions. There were no clinical or laboratory differences between patients treated with a macrolide (n = 172) and without (n = 85). Early corticosteroid therapy might reduce disease morbidity and prevent disease progression in MP pneumonia patients without side effects, and antibiotics may have limited effects on MP infection.

Malaria parasites increase their host erythrocyte’s permeability to obtain essential nutrients from plasma and facilitate intracellular growth. In the human P. falciparum pathogen, this increase is mediated by the plasmodial surface anion channel (PSAC) and has been linked to CLAG3, as encoded by one member of the conserved clag multigene family. Whether paralogs encoded by other clag genes also contribute to PSAC formation or serve unrelated roles remains unknown. Here, we generated transfectant lines carrying epitope-tagged versions of each CLAG. Each paralog colocalized with CLAG3, with concordant trafficking via merozoite rhoptries to the host erythrocyte membrane of newly-invaded erythrocytes. Each also exists within infected cells in at least two forms: an alkaline-extractable soluble form and a form integral to the host membrane. Like CLAG3, CLAG2 has a variant region cleaved by extracellular protease but CLAG8 and CLAG9 are protease-resistant. Paralog knockout lines, generated through CRISPR/Cas9 transfection, exhibited uncompromised growth in PGIM, a modified medium with more physiological nutrient levels; this finding is in marked contrast to a recently reported CLAG3 knockout parasite. CLAG2 and CLAG8 knockout lines exhibited compensatory increases in transcription of remaining clags and associated rhoph genes, yielding increased PSAC-mediated uptake to specific solutes. We also report distinct transport properties of these knockout lines, suggesting partially overlapping roles of CLAG paralogs in PSAC activity. We propose that the nutrient channel pore is formed by a higher order assembly of CLAG proteins at the host membrane.

Malaria rapid diagnosis test (RDT) is crucial for managing the disease, and the effectiveness of detection depends on parameters such as sensitivity and specificity of the RDT. Several factors can affect the performance of RDT. In this study, we focus on pfhrp2 sequence variation and its impact on RDTs targeted by antigens encoded by pfhrp2. Field samples collected during cross-sectional surveys in Tanzania were sequenced to investigate pfhrp2 sequence diversity and evaluate the impact on HRP2-based RDT performance. We observed significant mean differences in amino acid repeats between current and previous studies. Several new amino acid repeats were found to occur at different frequencies, including types AAY, AHHAHHAAN and AHHAA. Based on the abundance of types 2 and 7 amino acid repeats, the binary predictive model was able to predict RDT insensitivity by about 69 % in the study area. About 85% of the major epitopes targeted by Monoclonal antibodies (MAbs) in RDT were identified. Our study suggests that the extensive sequence variation in the pfhrp2 could contribute to reduced RDT sensitivity. The correlation between the different combinations of amino acid repeats and the performance of RDT in different malaria transmission settings should be investigated further.

Background/Purpose: In recent times, Sub-Sahara Africa (SSA) had been rated by the World Health Organization, (WHO), as the most malaria endemic region in the world. Evidence synthesis of the risk factors associated with malaria among children aged under-five in SSA is urgently needed. This would help to inform decisions that policy makers and executors in the region need to make for the effective distribution of scare palliative resources to curb the spread of the illness. This scoping review is aimed to identify studies that have used multivariate classical regression analysis to determine risk factors associated with malaria among children under-five years old in SSA. Methods/Design: The search terms followed PICOTS, (Population, Intervention, Comparator, Outcome, Timing, Setting), and were used in searching through the following databases: PubMed, MEDLINE, Web of Science, Cumulative Index of Nursing and Allied Health Literature (CINAHL), Scopus, and MeasureDHS. The databases were searched for published articles from January 1990 to December 2020. Results: Among the 1154 studies identified, only thirteen (13) studies met the study’s inclusion/exclusion criteria. Narrative syntheses were performed on the selected papers to synchronise the various risk factors identified. Factors ranging from child-related, (age, birth order and use of bed net), parental/household-related, (maternal age and education status, household wealth index) and community-related variables, (community wealth status, free bed net distribution), were some of the identified significant risk factors. Conclusion: It is timely to have a synthesis of risk factors that influence the malaria status of children under-five in SSA. The outcome of the review will increase the knowledge of the epidemiology of morbidity that will form the basis for designing efficient and cost-effective distribution of palliatives and controls of malaria in SSA.

El Niño is a quasi-periodic pattern of climate variability and extremes often associated with hazards and disease. While El Niño links to individual diseases have been examined, less is known about the cluster of multi-disease risk referred to as an ecosyndemic, which emerges during extreme events. The objective of this study was to explore a mapping approach to represent the spatial distribution of ecosyndemics in Piura, Peru at the district-level during the first few months of 1998. Using geographic information systems and multivariate analysis, two methodologies were employed to map disease overlap of 7 climate-sensitive diseases and construct an ecosyndemic index, which was then mapped and applied to another El Niño period as proof of concept. The main findings showed that many districts across Piura faced multi-disease risk over several weeks in the austral summer of 1998. The distribution of ecosyndemics were spatially clustered in western Piura among 11 districts. Furthermore, the ecosydemic index in 1998 when compared to 1983 showed a strong positive correlation, demonstrating the utility of the index. The study supports PAHO efforts to develop multi-disease based and interprogrammatic approaches to control and prevention, particularly for climate and poverty-related infections in Latin America and the Caribbean.

The use of disinfectants, particularly those containing quaternary ammonium compounds (QUACs), has dramatically escalated globally since the coronavirus disease 2019 pandemic. We report a case that highlights the risks associated with the ingestion of a low-concentration QUACs solution and emphasizes the importance of effective management in resolving severe lesions without sequelae. A 17-month-old boy experienced severe respiratory failure after ingesting a disinfectant containing benzalkonium chloride (BAC). The child was initially treated in a local emergency department and was subsequently transferred to a pediatric poison center. Upon evaluation, the child was found to have grade III-A corrosive esophageal lesions and chemical pneumonitis. Several complications, including massive pneumothorax and candidemia, occurred during the clinical course of the disease. However, with timely medical intervention and appropriate supportive care, the patient completely recovered without any long-term sequelae. The properties of BAC and a comprehensive management approach may have been responsible for the patient's full recovery despite the potential life-threatening effects of the ingestion of disinfectants.

Background: COVID-19 pneumonia caused by SARS-Cov-2 virus induces alveolar collapse and hypoxia that may become severe. The aim of the study is to analyze the effects of chest physiotherapy using a threshold valve in patients with acute respiratory failure due to COVID-19 pneumonia. Methods; Retrospective observational study, in hospitalized patients from March to May 2020. Breathing exercises were performed with a threshold valve of 10 cmH2O. Fraction of inspired oxygen, oxygen saturation, heart rate, respiratory rate and dyspnea were collected before and after the first session and at the end of the 5th day of chest physiotherapy treatment. Results: The final sample included 125 patients. Significant differences (p&lt;0.01) were found in the pre-post intervention SpO2/FiO2 ratio (250±88.4 vs 275.6±97.5, p&lt;0.001), reaching 354.4±110.2 after 5 days of therapy (p&lt;0.001 with respect to baseline). Mean baseline respiratory, heart rate and level of dyspnea measure by the Borg scale did not change during the technique performance. In patient maneuvers with FiO2&gt;0.4, the SaO2/FiO2 ratio increase was higher than in patients with milder severity (46.85 ± 77.69, p&lt;0.01). Conclusions: Chest physiotherapy with a 10 cmH2O threshold valve is a safe and tolerated intervention with short-term improvement in oxygenation in patients with COVID-19 pneumonia.

The emergence of new SARSCoV-2 variants can affect vaccine efficacy, laboratory diagnosis and therapies already available, triggering interest in the search for antiviral agents for SARSCoV-2 infections. Ribavirin (RBV) is a broad-spectrum antiviral with demonstrated in vitro activity against multiple viruses, including SARSCoV-2. Methods. This retrospective study evaluated the dynamic and viral clearance of SARSCoV-2 in hospitalized adult participants (PTs) with COVID-19 pneumonia who received RBV aerosol within a compassionate use study. Was also assessed the impact of RBV on the clinical outcome and the mutational profile of SARSCoV-2. Results. The median RNA values measured in nine PTs included in the study de-creased from baseline to discharge (at BL, threshold cycle (Ct)=22.4, IQR 19.84-5.07; at discharge, Ct=27.92, IQR 26.43-36.11). Seven/9 PTs experienced a clinical improvement, while two PTs deceased during hos-pitalization. In PTs with a favorable outcome the virus clearance rate at discharge was 28.6%. The cumulative clearance rate was 71.4% within day 14th from discharge. A mutational pattern after RBV was detected in 3/5 PTs in whom was available whole genome sequencing. Conclusions. RBV may limit SARSCOV-2 replication resulting in a favorable clinical outcome. Ribavirin may also contribute to the mutational spectrum of SARSCoV-2.

Genomic analysis indicates that SARS-CoV-2 is most related to RaTG13, a beta corona virus derived from bats by 96% ¹. At present, RaTG13 is only available on the public database in the form of a genome sequence. The genome of RaTG13 (MN996532.1) was sequenced from the RNA of a bat faecal swab collected in 2013 from Yunnan, China, however the exact location is not mentioned. Since RaTG13 is one of the main supports for SARS-CoV-2 to have a natural origin, it is of utmost importance to understand the sample location. RNA dependent RNA polymerase (RdRp) sequence of RaTG13 shows that it is 100% similar to that of bat corona virus BtCoV/4991 and 98.7-98.9% similar to SARS-CoV-2 RdRp ². BtCoV/4991 was described to be a SARS-like (SL-) corona virus from bat faeces sampled in an abandoned mine from Mojiang ². Both the publications ^1,2 are authored by Dr. Zheng-li Shi (Z-L Shi), who is described as the bat woman of China ³. However, BtCoV/4991 has not been mentioned by Zhou et al 2020 ¹ where novel corona virus was first described. Based on the RdRp sequence similarities, similarities in sample collection dates, sample locations, and the fact that RaTG13 is mentioned synonymous to BtCoV/4991 on the Chinese bat database, it is predicted that RaTG13 and BtCoV/4991 originate from the same sample. The sample, bat faecal swab was collected in 2013 from an abandoned mineshaft in Mojiang by Dr. Shi and her work group. In 2012, in a Mojiang mineshaft, six mine workers suffered from atypical pneumonia and three of them died. These workers were engaged in the work of clearing debris from a mineshaft which had a lot of bats and bat faeces ^3,4. A detailed health investigation indicated that the miners suffered from atypical pneumonia mostly of the viral origin ⁴. Therefore, in the light of the present Covid-19 caused by SARS-CoV-2, the fact that its phylogenetic neighbour RaTG13 originated from bat faeces collected from a mineshaft, which was also the origin of pneumonia-like disease in miners in 2012, should be noted.

The natural history of COVID-19 caused by SARS-CoV-2 is extremely variable, ranging from asymptomatic infection, to pneumonia, and to complications eventually fatal. We propose here the first model, explaining how the outcome of first, crucial 10-15 days after infection, hangs on the balance between the cumulative dose of viral exposure and the efficacy of the local innate immune response (natural IgA and IgM antibodies, MBL). If SARS-CoV-2 runs the blockade of this innate immunity and spreads from the upper airways to the alveoli in the early phases of the infections, it can replicate with no local resistance, causing pneumonia and releasing high amounts of antigens. The delayed and strong adaptive immune response (high affinity IgM and IgG antibodies) that follows, causes severe inflammation and triggers mediator cascades (complement, coagulation, and cytokine storm) leading to complications often requiring intensive therapy and being, in some patients, fatal. Strenuous exercise and high flow air in the incubation days and early stages of COVID-19, facilitates direct penetration of the virus to the lower airways and the alveoli, without impacting on the airway’s mucosae covered by neutralizing antibodies. This allows the virus to bypass the efficient immune barrier of the upper airways mucosa in young and healthy athletes. In conclusion, whether the virus or the adaptative immune response reach the lungs first, is a crucial factor deciding the fate of the patient. This “quantitative and time-sequence dependent” model has several implications for prevention, diagnosis, and therapy of COVID-19.

Acute respiratory distress syndrome (ARDS) is caused by infectious insults, such as pneumonia from various pathogens or related to other noninfectious events. Clinical and histopathologic characteristics are similar across severely affected patients, suggesting that a common mode of immune reaction may be involved in the immunopathogenesis of ARDS. There may be etiologic substances that have an affinity for respiratory cells and induce lung cell injury in cases of ARDS. These substances originate not only from pathogens, but also from injured host cells. At the molecular level, these substances have various sizes and biochemical characteristics, classifying them as protein substances and non-protein substances. Immune cells and immune proteins may recognize and act on these substances, including pathogenic proteins and peptides, depending upon the size and biochemical properties of the substances (this theory is known as the protein-homeostasis-system hypothesis). The severity or chronicity of ARDS depends on the amount of etiologic substances with corresponding immune reactions, the duration of the appearance of specific immune cells, or the repertoire of specific immune cells that control the substances. Therefore, treatment with early systemic immune modulators (corticosteroids and/or intravenous immunoglobulin) as soon as possible may reduce aberrant immune responses in the potential stage of ARDS.

Ion channels serve many cellular functions including ion homeostasis, volume regulation, signaling, nutrient acquisition, and developmental progression. Although the complex lifecycles of malaria parasites necessitate ion and solute flux across membranes, whole genome sequencing of the human pathogen, Plasmodium falciparum, revealed remarkably few orthologs of known ion channel genes. Contrasting with this, biochemical studies have implicated channel-mediated flux of ions and nutritive solutes across several membranes in infected erythrocytes. Here, I review advances in the cellular and molecular biology of ion channels in malaria parasites. These studies have implicated novel parasite genes in the formation of at least two ion channels, with additional ion channels likely present at various membranes and parasite stages. Computational approaches that rely on homology to known channel genes from higher organisms will not be very helpful in identifying the molecular determinants of these activities. Given their unusual properties, novel molecular and structural features, and essential roles in pathogen survival and development, parasite channels should be promising targets for therapy development.

The malaria parasite resides within erythrocytes during one stage of its life cycle. During this intraerythrocytic period, the parasite ingests the erythrocyte cytoplasm and digests approximately two-thirds of the host cell hemoglobin. This digestion occurs within a lysosome-like organelle called the digestive vacuole. Several proteases are localized to the digestive vacuole and these proteases sequentially breakdown hemoglobin into small peptides, dipeptides, and amino acids. The peptides are exported into the host cytoplasm via the chloroquine-resistance transporter and an amino acid transporter has also been identified on the digestive vacuole membrane. The environment of the digestive vacuole also provides appropriate conditions for the biocrystallization of toxic heme into non-toxic hemozoin by a poorly understood process. Hemozoin formation is an attribute of Plasmodium and Haemoproteus and is not exhibited by other intraerythrocytic protozoan parasites. The efficient degradation of hemoglobin and detoxification of heme likely plays a major role in the high level of replication exhibited by malaria parasites within erythrocytes. Unique features of the digestive vacuole and the critical importance of nutrient acquisition provide therapeutic targets for the treatment of malaria.

In Brazil, malaria transmission is mostly confined to the Amazon, where substantial progress has been achieved towards disease control in the past decade. Vector control has been historically considered a fundamental part of the main malaria control programs implemented in Brazil. However, the conventional vector-control tools have been insufficient to eliminate local vector populations due to the complexity of the Amazonian rainforest environment and ecological features of malaria vector species in the Amazon, especially Anopheles darlingi. Malaria elimination in Brazil and worldwide eradication will require a combination of conventional and new approaches that takes into account the regional specificities of vector populations and malaria transmission dynamics. Here we present an overview on both conventional and novel promising vector-focused tools to curb malaria transmission in the Brazilian Amazon. If well designed and employed, these new vector-based approaches may improve the implementation of malaria-control programs, particularly in remote or difficult-to-access areas and in regions where existing interventions have been unable to eliminate disease transmission. However, much effort still has to be put on research expanding the knowledge of neotropical malaria vectors to set the steppingstones for the development of such innovative tools.

The mosquito microbiota reduces the vector competence of Anopheles to Plasmodium and affects host fitness, it is therefore considered as a potential target to reduce malaria transmission. While immune induction, secretion of antimicrobials and metabolic competition are three typical mechanisms of microbiota-mediated protection against invasive pathogens in mammals, the involvement of metabolic competition or mutualism in mosquito-microbiota and microbiota-Plasmodium interactions has not been investigated. Here, we describe a metabolome analysis of the midgut of An. coluzzii provided with a sugar-meal or a blood-meal, under conventional or antibiotic-treated conditions. We observed that the antibiotic treatment affects the tricarboxylic acid cycle and nitrogen metabolism, notably resulting in decreased abundance of free amino acids. Linking our results with published data, we identified candidate pathways which may participate in microbiota/Plasmodium interactions via metabolic interactions or immune modulation.

The paper demonstrates the analysis of Corona Virus Disease based on a CNN probabilistic model. It involves a technique for classification and prediction by recognizing typical and diagnostically most important CT images features relating to Corona Virus. The main contributions of the research include predicting the probability of recurrences in no recurrence (first time detection) cases at applying our proposed Convolution neural network structure. The Study is validated on 2002 chest X-ray images with 60 confirmed positive covid19 cases and (650 bacterial – 412 viral -880 normal) x-ray images. The proposed CNN compared with traditional classifiers with proposed CHFS feature extraction model. The experimental study has done with real data demonstrates the feasibility and potential of the proposed approach for the said cause. The result of proposed CNN structure has been successfully done to achieve 98.20% accuracy of covid19 potential cases with comparable of traditional classifiers.

Necrotizing pneumonia due to Methicillin-Resistant Staphylococcus Aureus (MRSA) is devastating and difficult to treat in preterm infants. We report a case of severe MRSA necrotizing pneumonia in a preterm infant. As an add-on rescue therapy to vancomycin, linezolid rapidly cured this case after the failure of vancomycin plus rifampicin. This rapid cure suggests that adjunctive rather than rescue linezolid may be considered in such cases.

Immune response stimulation may be an adjuvant to antimicrobial treatment. Here, we evaluated the impact of immune response modification by lysophosphatidylcholine (LPC) combined with imipenem or ceftazidime in murine models of peritoneal sepsis (PS) and pneumonia by Pseudomonas aeruginosa. Imipenem and ceftazidime-susceptible strain (Pa39), and imipenem and ceftazidime-resistant strain (Pa238) were used. Ceftazidime pharmacokinetic and pharmacodynamic parameters were determined. Therapeutic efficacy, and TNF-α and IL-10 levels were determined in murine models of PS and pneumonia by Pa39 and Pa238 treated with LPC, imipenem or ceftazidime, alone or in combination. In PS model, LPC+ceftazidime reduced spleen and lungs Pa238 concentrations (-3.45 and -3.56 log10 CFU/g; P<0.05) than ceftazidime monotherapy, while LPC+imipenem maintained the imipenem efficacy (-1.66 and -1.45 log10 CFU/g; P>0.05). In pneumonia model, LPC+ceftazidime or LPC+imipenem reduced lungs Pa238 concentrations (-2.37 log10 CFU/g, P=0.1, or -1.35 log10 CFU/g, P=0.75). For Pa39 no statistically significant difference has been observed in PS and pneumonia models between combined therapy and monotherapy. Moreover, LPC+imipenem and LPC+ceftazidime decreased and increased significantly TNF-α and IL-10 levels, respectively, in comparison with untreated controls and monotherapies. These results demonstrate the impact of immune response modification by LPC plus antibiotics on the prognosis of infections by ceftazidime-resistant P. aeruginosa.

Malaria is rare in Europe, but it is a medical emergency and programs for its control should ensure access to early diagnosis and prompt treatment within 24-48 h of the symptom’s onset. The consistent number of imported malaria cases and the risk of reappearance of autochthonous cases stimulated laboratories in non-endemic countries to evaluate diagnostic methods/algorithms: microscopy remains the gold standard, but with limitations. RDTs have greatly expanded the ability to diagnose malaria for rapid results due to simplicity and low cost, but they lack sensitivity and specificity. PCR-based assays provide more relevant information but need well-trained technicians. According to WHO global Technical Strategy for Malaria 2016-2030, the future direction for a rapid diagnosis is the development of Point-Of-Care Testing, which would be helpful for prompt/accurate treatment and for preventing the diseases spread. Despite the limitations of current diagnostic methods, they play important roles in dealing with the global malaria situation, including decreasing its incidence. Recently evidence suggested that Artificial Intelligence could be utilized for assisting pathologists in malaria diagnosis. Future studies need to be conducted to see whether this system can be used for routine malaria diagnostic procedures.

The Duffy protein, a transmembrane molecule, functions as a receptor for various chemokines and facilitates attachment between the reticulocyte and the Plasmodium Duffy antigen-binding protein. Duffy expression correlates with the Duffy receptor gene for the chemokine, located on chromosome 1, and exhibits geographical variability worldwide. Traditionally, researchers have described the Duffy negative genotype as a protective factor against phenotypic malaria expression. However, recent studies suggest this microorganism's evolution potentially diminishes this protective effect. Nevertheless, there is currently insufficient global data to demonstrate this phenomenon. This study aimed to evaluate the relationship between the Duffy genotype/phenotype and the prevalence of Plasmodium vivax infection. The protocol for the systematic review was registered in PROSPERO as CRD42022353427 and involved reviewing published studies from 2012 to 2022. Medline, Web of Science, Scopus, and Scielo databases were consulted. Assessments of study quality were conducted using the STROBE and GRADE tools. A total of 34 studies were included, with Africa accounting for most recorded studies. The results varied significantly regarding the relationship between the Duffy genotype/phenotype and Plasmodium vivax invasion. Some studies predominantly featured the negative Duffy genotype yet reported no malaria cases. Other studies identified minor percentages of infections. Conversely, certain studies observed a higher prevalence (99%) of Duffy-negative individuals infected with Plasmodium vivax. In conclusion, no evidence of a gender-specific distribution of malaria between Duffy-negative men and women was found. However, evidence supports that the homozygous Duffy genotype positive for the A allele (FY*A/*A) is associated with a higher incidence of Plasmodium infection. Furthermore, the negative Duffy genotype does not confer protection against this disease.

Plasmodium species that cause malaria, a disease responsible for about half a million deaths per annum despite concerted efforts to combat it. The causative agent depends on type III beta phosphatidylinositol 4-kinase (PPI4K) during the development of merozoite. PPI4K is the only clinically validated Plasmodium kinase so far and its inhibitors are effective both in vitro and in vivo. In this work, a small library of ~22 000 fragments was virtually screened using PPI4K homology model to discover potential ligands of the enzyme. 16 virtual hits were selected based on ≤ -9.0 kcal/mol binding energy cut off and were subjected to similarity and substructure searching after they had passed PAINS screening. The derivatives obtained showed improved binding energies, which ranged from -10.00 to -13.80 kcal/mol. Moreover, the topmost ranking compound 31, with interesting drug-like quality was stable within the protein’s binding cavity during the 10 ns molecular dynamics simulation period. In addition, analysis of its binding pose revealed some unique binding interactions with PPI4K active site residues as the basis for the observed improved binding affinity. Overall, compound 31 appears to be a viable starting point for the development of PPI4K inhibitors with antimalarial activity.

(1) Background: Neglected tropical diseases (NTDs) have been overlooked on the global health agenda and in the priorities of national systems in low- and middle-income countries (LMICs). In 2012, the Sustainable Development Goals (SDGs) were created to ensure healthy lives and promoting well-being for all. This roadmap set out to accelerate work to overcome the global impact of NTDs. Almost a decade has passed since NTDs were re-launched as a global priority. Investment in research and development, as well as the production of scientific literature on NTDs, is expected to have increased significantly. (2) Methods: A bibliometric analysis of the scientific production of Latin America and the Caribbean (LAC) was carried out in relation to 19 endemic NTDs. These data were compared with the scientific production in malaria, tuberculosis and HIV / AIDS. The database available from Thomson Reuters Web of Science (WoS) was used. In addition, the average annual growth percentage was calculated for each disease. (3) Results: In the last decade, the NTDs with the highest number of publications in the world were dengue and leishmaniasis. The United States was the most prolific country in the world in 15 out of 19 NTDs analyzed. In the LAC region, Brazil was the largest contributor for 16 of the 19 NTDs analyzed. Arboviral diseases showed the highest average annual growth. The number of publications for malaria, tuberculosis and HIV /AIDS was considerably higher than for NTDs. The contribution of most LAC countries, especially those considered as LMICs, is inadequate and does not reflect the relevance of NTDs for the public health of the population. (4) Conclusion: This is the first bibliometric analysis to assess the trend of scientific documents on endemic NTDs in LAC. Our results could be used by decision makers both to strengthen investment policies in research and development in NTDs.

Growth environment greatly alters many facets of pathogen physiology, including pathogenesis and antimicrobial tolerance. The importance of host-mimicking environments for attaining an accurate picture of pathogen behaviour is widely recognised. Whilst this recognition has translated into the extensive development of artificial cystic fibrosis (CF) sputum medium, attempts to mimic the growth environment in other respiratory disease states have been completely neglected. The composition of the airway surface liquid (ASL) in different pulmonary diseases is far less well characterised than CF sputum, making it very difficult for researchers to model these infection environments. In this review we discuss the components of human ASL, how different lung pathologies affect ASL composition, and how different pathogens interact with these components. This will provide researchers interested in mimicking different respiratory environments with the information necessary to design a host-mimicking medium, allowing for better understanding of how to treat pathogens causing infection in these environments.

The fate of critically sick patients with infections in intensive care units (ICUs) is significantly influenced by antimicrobial resistance, which has become a serious concern in developing nations. This observational study was conducted at the IBN Sina Specialised Hospital in Dhaka, Bangladesh, over a 12-month period from January 2021 to December 2021, in order to track the pattern of antibiotic resistance among the patients admitted to the intensive care unit (ICU). Aspiration pneumonia (29%) and diabetes mellitus (24%), among 200 patients, were the most common main diagnoses. 65 samples (or 26%) of the 250 samples had 85 bacteria identified from them. Urine (14.12%) and tracheal aspirate (64.71%) were the most frequently found sites of infection. In the sample from the tracheal aspirate, Pseudomonas spp. (30.59%), Escherichia coli (24.71%), Acinetobacter spp. (20%), and Klebsiella spp. (14.12) were the most frequently isolated microorganisms. The following antibiotics were shown to have the highest overall patterns of resistance: levofloxacin (68.24), amikacin (64.71), meropenem (49.41), ceftazidime (75.29), ciprofloxacin (78.82), and gentamicin (82.35). The most effective antibiotic against Klebsiella species was meropenem (64.61%), while Acinetobacter species were mostly susceptible to cotrimoxazole (64.67%) and piperacillin + tazobactam (60.50%). Most susceptible to netilmicin (70.48%) and meropenem (49.32%) were Escherichia coli, while Pseudomonas spp. were mostly responsive to colistin (55.14%) and netilmicin (52.25%). Antibiotic resistance is common among intensive care unit (ICU) patients, and most isolated microbes have resistance to traditional medicines.

Background: Data on the benefits of rapid microbiological testing on antimicrobial consumption (AC) and antimicrobial resistance patterns(ARP) are scarce. We evaluated the impact of a protocol based on rapid techniques on AC and ARP in intensive care (ICU) patients. Methods: Retrospective pre(2018) and post-intervention(2019-21) study in ICU patients. A rapid diagnostic algorithm was applied from 2019 in patients with lower respiratory tract infection. Incidence of nosocomial infection, ARP, and AC as DDD(defined daily dose) were monitored. Results: A total of 3635 patients were included, 987(pre-intervention) and 2648(post-intervention). A median age was 60 years, 64% male, with APACHE II of 19 points and SOFA of 3 points. Overall ICU mortality of 17.2% without differences between the periods. An increase in the number of infections was observed in the post-intervention period(44.5% vs 17.9%, p<0.01), especially due to an increase in ventilator-associated pneumonia(44.6% vs 25%,p<0.001). AC decreased from 128.7 DDD in 2018 to 66.0 DDD in 2021(Rate Ratio=0.51). A recovery of P.aeruginosa susceptibility of 23% for Piperacillin/tazobactam and 31% for Meropenem was observed. Conclusion: The implementation of an algorithm based on rapid microbiological diagnostic techniques allowed a significant reduction in AC and ARP without affecting the prognosis of critically ill patients.

There are limited proven therapies for the treatment of COVID-19. Vitamin C’s antioxidant, anti-inflammatory and immunomodulating effects, make it a potential therapeutic candidate, both for the prevention and amelioration of COVID-19 infection, and as an adjunctive therapy in the critical care of COVID-19, supporting anti-inflammatory treatment. This literature review focuses on vitamin C deficiency in respiratory infections including COVID-19; the mechanism of action in infectious disease and adrenal function supporting the anti-inflammatory actions of glucocorticosteroids: its role in preventing and treating colds and pneumonia and its role in treating sepsis and COVID-19. The evidence to date indicates that oral vitamin C (2-8g/d) may reduce incidence and duration of respiratory infections and intravenous vitamin C (2-24g/d) has been shown to reduce mortality, Intensive Care Unit and hospital stays, time on mechanical ventilation in severe respiratory infections. Further trials are urgently warranted. Given the favourable safety profile and low cost of vitamin C, and frequency of vitamin C deficiency in respiratory infections it may be worthwhile testing patients’ vitamin C status and treating accordingly with intravenous use within ICUs and orally with doses between 2 and 8g/day in hospitalised and infected persons.

Influenza virus infection causes severe respiratory illness in people worldwide, disproportionately affecting infants. The immature respiratory tract coupled with the developing immune system is thought to synergistically play a role in the increased disease severity in younger age groups. Although vaccines remain the best solution for protecting this vulnerable population, no vaccines are available for those under 6 months, and for infants aged 6 months to 2 years, the vaccine elicits a dampened immune response. Dampened immune responses may be due to unique features of the infant immune system and a lack of pre-existing immunity. Unlike older children and adults, the infant immune system is Th2 skewed and has less antigen presenting cells and soluble immune factors. Paradoxically, we know that a person’s first infection with the influenza virus during infancy or childhood leads to the establishment of life-long immunity toward that particular virus strain. This is called influenza imprinting. To provide better protection against influenza virus infection and disease in infants, more research must be conducted to understand the imprinting event. We contend that by understanding influenza imprinting in the context of the infant immune system and the infant’s immature respiratory tract, we will be able to design more effective influenza vaccines for both infants and adults. Working through the lens of imprinting, using infant influenza animal models such as mice and ferrets, which have proven useful for infant immunity studies, we will gain a better understanding of imprinting and its implications regarding vaccine design. This review examines literature regarding infant immune development, current vaccine strategies, respiratory development, and the importance of researching the imprinting event in infant animal models to develop more effective and protective vaccines for young children.

Clinical metagenomics (CMg), referred to as the application of next-generation sequencing (NGS) to clinical samples, is a promising tool for the diagnosis of hospital-acquired pneumonia (HAP). Indeed, CMg allows identifying pathogens and antibiotic resistance genes (ARGs), thereby providing the information required for the optimization of the antibiotic regimen. Hence, provided that CMg would be faster than conventional culture, the probabilistic regimen used in HAP could be tailored faster, which should lead to an expected decrease of mortality and morbidity. While the inference of the antibiotic susceptibility testing from metagenomic or even genomic data is challenging, a limited number of antibiotics are used in the probabilistic regimen of HAP (namely beta-lactams, aminoglycosides, fluoroquinolones, glycopeptides and oxazolidinones). Accordingly in the perspective of applying CMg to the early diagnostic of HAP, we aimed at reviewing the performances of whole genomic sequencing (WGS) of the main HAP-causing bacteria (Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter baumannii, Stenotrophomonas maltophilia and Staphylococcus aureus) for the prediction of susceptibility to the antibiotic families advocated in the probabilistic regimen of HAP.

Background/Objectives: Community-acquired pneumonia (CAP) is a common emergency presentation in Australia, with the choice of admitting specialty unit often influenced by pneumonia severity and comorbidities. However, it remains unclear whether there are between-specialty differences in patient characteristics and outcomes. We sought to address this issue by investigating the characteristics and outcomes of CAP patients admitted to General Medicine (GM) versus Respiratory units.Methods: This retrospective observational study utilised data from the two largest metropolitan hospitals in South Australia, encompassing all non-COVID-19-related CAP admissions throughout 2021 to 2023. Hospital length of stay (LOS), in-patient and 30-day mortality, and 30-day readmission rates were assessed by propensity-score-matching (PSM) with using 14 variables.Results: Of the 3,004 cases of non-COVID-19 CAP admitted across the two hospitals during the study period, 2,673 (71.8%) were admitted under GM units and 331 (9.1%) under Respiratory units. GM patients were, on average, a decade older, presented with a significantly higher burden of comorbidities, exhibited a greater prevalence of frailty and had higher pneumonia severity compared to those admitted under a Respiratory unit, (P

Chest trauma is one of the most serious and difficult injuries, with various complications that can lead to ventilation - perfusion (V/Q) mismatch and systemic hypoxia. We are presenting a case of 53 – year - old male with no comorbidities or chronic therapy, who was admitted to the Intensive Care Unit due to severe respiratory failure after chest trauma. He developed right - sided pneumothorax and then thoracic drain was placed. On admission, the patient was hemodynamically unstable and tachypneic. The patient was intubated and mechanically ventilated, febrile (38.9°C) and unconscious. A lung CT showed massive non-ventilated areas predominantly in the right lung. He was ventilated with PEEP of 10 cmH2O with a FiO2 of 0.6 – 0.8. Empirical broad-spectrum antimicrobial therapy was immediately initiated. Both high FiO2 and moderate PEEP were maintained and adjusted according to the current blood gas values and oxygen saturation. After Stenotrophomonas maltophilia was identified and treated with sulfamethoxazole/trimethoprim his general condition gradually improved, and he was weaned from mechanical ventilation. In conclusion, both ventilatory and antibiotic therapy were needed to improve oxygenation and outcome of the patient with pneumonia due to the resistant S. maltophilia with V/Q mismatch.

The alkaloid tazopsine 1 was introduced in the late 2000's as a novel antiplasmodial hit compound active against Plasmodium falciparum hepatic stages, with potential to develop prophylactic drugs based on this novel chemical scaffold. However, the structural determinants of tazopsine 1 bioactivity, together with the exact definition of the pharmacophore, remained elusive, impeding further development. We found that the antitussive drug dextromethorphan (DXM) 3, although lacking the complex pattern of stereospecific functionalization of the natural hit, was harboring significant antiplasmodial activity in vitro despite suboptimal prophylactic activity in a murine model of malaria, which precluded its direct repurposing against malaria. The targeted N-alkylation of nor-DXM 15 delivered a small library of analogues with greatly improved activity over DXM 3 against P. falciparum asexual stages. Amongst these, N-2’-pyrrolylmethyl-nor-DXM 16i showed a 2- to 36-fold superior inhibitory potency compared to tazopsine 1 and DXM 3 against parasite liver and blood stages, with 760 ± 130 nM and 2.1 ± 0.4 µM IC50 values, respectively, as well as liver/blood phase selectivity of 2.8. Furthermore, cpd. 16i showed a 5 to 8-fold increase of activity relatively to DXM 3 against P. falciparum stages I-II and V gametocytes, with 18.5 µM and 13.2 µM IC50 values, respectively. Cpd. 16i can thus be considered a promising novel hit compound against malaria in the ent-morphinan series with putative pan-cycle activity, paving the way for further therapeutic development (e. g., investigation of its prophylactic activity in a mouse model of malaria).

There is an overarching need to find alternative treatment options for malaria and this quest is more pressing in current times due to the morbidity and mortality data arising from most endemic countries and partially owing to the fact that the SARS-Cov-2 pandemic has diverted much public health attention. Additionally, the therapeutic options available for malaria has been severely threatened with the emergence of resistance to almost all existing drugs by the human malaria parasite. The Artemisinin Combination Therapies (ACTs) which hitherto have been the mainstay for malaria have encountered resistance in South East Asia, a notorious ground zero for the emergence of antimalarial drug resistance. This review analyses few key druggable targets of the parasite and the potential to leverage strategic inhibitors to mitigate the scourge of malaria by providing a concise assessment of the essential proteins of the malaria parasite that could serve as targets. Furthermore, this work provides a summary of the advances made in malaria parasite biology and the potential to leverage such findings for antimalarial drug production.

Malaria is a serious infection affecting millions of people in Africa. Our study investigated the personal preferences and applications of antimalarial medicines in Ghana. Based on over 1000 questionnaires distributed in Ghana from January to May 2019, we noticed that although Western medications to fight this disease are widely available, most patients in Ghana prefer treatment with locally produced herbal remedies. This preference appears to be due to a combination of traditional venues for obtaining medicines “on the street” rather than in licensed pharmacies, trust in local and “green” products, extensive advertisement of such local products, and an inherent distrust of imported and synthetic or unnatural medicines. Going local and natural is a trend also observed in other countries across the globe, and adds to the acceptance or rejection of drugs regardless of their activity or toxicity. In fact, adverse side effects associated with herbal remedies, such as general weakness and swollen, sore mouth, do not seem to deter the respondents of this study in Ghana. We propose a combination of (a) increasing public awareness of the benefits of modern medicine and (b) an improvement and control of the quality of herbal remedies to raise the standard of malaria treatment in countries such as Ghana.

Abstract: Background: Our goal was to evaluate whether wearing personal protective equipment (PPE) such as an N95, or a surgical mask during the (COVID-19) pandemic had really reduced the cases of influenza in the state of Wisconsin. Methods: Respiratory Virus Surveillance Reports from the Wisconsin Department of Health Services (DHS) and the Centers for Disease Control and Prevention (CDC) were used to compare the rates of Influenza during the seasons of 2018-2019 and 2020-2021. Results: The number of cases, hospitalizations, and mortality rates with Influenza had significantly decreased in the 2020-2021 season compared to the Influenza season of 2018-2019. Discussion: Reducing the burden of influenza illnesses, hospitalizations, and deaths on the health care system is imperative. Wearing masks should be addressed for the most vulnerable.

Advancements in deep learning and availability of medical imaging data have led to use of CNN based architectures in disease diagnostic assisted systems. In spite of the abundant use of reverse transcription-polymerase chain reaction (RT-PCR) based tests in COVID-19 diagnosis, CT images offer an applicable supplement with its high sensitivity rates. Here, we study classification of COVID-19 pneumonia (CP) and non-COVID-19 pneumonia (NCP) in chest CT scans using efficient deep learning methods to be readily implemented by any hospital. We report our deep network framework design that encompasses Convolutional Neural Networks (CNNs) and bidirectional Long Short Term Memory (biLSTM) architectures. Our study achieved high specificity (CP: 98.3%, NCP: 96.2% Healthy: 89.3%) and high sensitivity (CP: 84.0%, NCP: 93.9% Healthy: 94.9%) in classifying COVID-19 pneumonia, non-COVID-19 pneumonia and healthy patients. Next, we provide visual explanations for the CNN predictions with gradient-weighted class activation mapping (Grad-CAM). The results provided a model explainability by showing that Ground Glass Opacities (GGO), indicators of COVID-19 pneumonia disease, were captured by our CNN network. Finally, we have implemented our approach in three hospitals proving its compatibility and efficiency.

The gut microbiota has recently been associated with susceptibility/resistance to malaria in animal models and humans, yet the impact of the gut microbiota on the risk of a malaria attack remains to be assessed. This study aims at assessing the influence of the gut microbiota on malaria attacks and Plasmodium parasitæmia in children living in a malaria-endemic area in Mali. Three hundred healthy children were included in a 16-months cohort study in Bandiagara. Their gut bacteria and fungi community structures were characterised via 16S and ITS metabarcoding from stool samples collected at inclusion. Clinician team monitored the occurrence of malaria attacks. Asymptomatic carriage of Plasmodium was assessed by qPCR. Over the 16-month period, 107 (36%) children experienced at least one occurrence of malaria attacks, and 82 (27%) at least one asymptomatic Plasmodium parasitæmia episode. A higher gut bacteria richness was independently associated with susceptibility to asymptomatic parasitæmia episodes and malaria attacks; while the Shannon H diversity and Chao-1 richness index of gut fungi community structure was relatively homogeneous in children who were and were not infected with P. falciparum. Using a linear discriminant effect size analysis of operational taxonomic units assigned to the species level, 17 bacteria, including Clostridiaceae, Eubacteriaceae, Senegalimassilia sp., Atopobiaceae and Lachnosipraceae, and seven fungi, including Dioszegia fristigensis, Ogataea polymorpha and Cutaneotrichosporon cyanovorans, were associated with susceptibility; whereas eight bacteria, including, Bifidobacterium spp., Weissela confusa and Peptostreptococcacea, and 3 fungi, Malassezia sp., Niesslia exosporoides, and Didymocrea leucaenae, were associated with resistance to malaria. Moreover, 15 bacteria, including Coproccus eutactus, Terrisporobacter petrolearius, Klebsiella pneumoniae and Ruminococcaceae, and 13 fungi, including Wallemia mellicola, were associated with susceptibility, whereas 19 bacteria, including Bifidobacterium spp., Bacteroides fragilis, Peptostreptococcacea, and Lactobacillus ruminis, and three fungi, including Cryptococcus neoformans, were associated with resistance to asymptomatic Plasmodium parasitæmia episodes. Further studies are needed to confirm these findings that point the way towards strategies aiming to reduce the risk of malaria by modulating gut microbiota components in at-risk populations.

Current microbiological methods for pneumonia diagnosis require invasive specimen collection and time-consuming analytical procedures. There is a need for less invasive and faster methods to detect lower respiratory tract infection. The analysis of volatile metabolites excreted by pathogenic microorganisms provides the basis for developing such a method. Given the synergistic role of Candida albicans in increasing the virulence of pathogenic bacteria causing pneumonia and the cross-kingdom metabolic interactions between microorganisms, we compare the emission of volatiles from Candida albicans yeasts and the bacteria Staphylococcus aureus using single and mixed co-cultures and apply that knowledge to human in vivo investigations. Gas-chromatography-mass spectrometry (GC-MS) analysis resulted in the identification of sixty-eight volatiles that were found to have significantly different levels in cultures compared to reference medium samples. Certain volatiles found in co-culture originated mainly from C. albicans metabolism (e.g., isobutyl acetate), whereas other volatiles primarily came from S. aureus (e.g., ethyl 2-methylbutyrate). Isopentyl valerate reflects synergic interactions of both microbes, as its level in co-cultures was found to be approximately three times higher than the sum of its amounts in monocultures. Hydrophilic-lipophilic balanced (HLB) coated meshes for thin-film microextraction (TFME) were used to pre-concentrate volatiles directly from bronchoalveolar lavage (BAL) specimens collected from patients suffering from ventilation-associated pneumonia (VAP) that was caused explicitly by C. albicans and S. aureus. GC-MS analyses confirmed the existence of in vitro-elucidated microbial VOCs in human specimens. Significant differences in BAL-extracted amounts respective to the pathogen causing pneumonia were found. The model in vitro experiments provided evidence that cross-kingdom interactions between pathogenic microorganisms affect the synthesis of the volatile compounds. The TFME meshes coated with HLB particles proved to be suitable for extracting VOCs from human material, enabling the translation of in vitro experiments on the microbial volatilome to the in vivo situation involving infected patients. This indicates the direction that should be taken for further clinical studies on VAP diagnosis based on volatile analysis.

This article introduces a new MfEIT UDESC Mark I system, which consists of a 32-electrode setup featuring a modified Howland current source, low cost, portable and non radiation. The system is capable of reconstruction of electrical conductivity tomographic images at a rate of 30.624 frames per second and about 5 minutes for imaging. The current source employs 0.5 mA, adjacent current application pattern with frequencies ranging from 10 kHz to 1 MHz. The article outlines the hardware, firmware, and software design specifications, which include the design of the current source, calibration procedures, and image reconstruction process. Tomographic images of conductivity were reconstructed in ex vivo healthy pig lungs and those with pneumonia, as a proof of concept for future applications in live pigs. The high spectral power density, combined with real-time system calibration provides clinical advantages in veterinary medicine. The goal is to identify lung areas affected by Mycoplasma hyopneumoniae in pigs, through the analysis of electrical conductivity difference, offering a valuable tool to assist veterinarians for to obtain images of respiratory diseases. The reconstruction method (GREIT) was evaluated with experimental data and It was compared with the Gauss-Newton and Total Variation methods, where GREIT proved to be superior.

One of the critical tools for early detection and subsequent evaluation of the incidence of lung diseases is chest radiography. At a time when the speed and reliability of results, especially for COVID-19 positive patients, is important, the development of applications that would facilitate the work of untrained staff involved in the evaluation is also crucial. Our model takes the form of a simple and intuitive application, into which you only need to upload X-rays: tens or hundreds at once. In just a few seconds, the physician will determine the patient's diagnosis, including the percentage accuracy of the estimate. While the original idea was a mere binary classifier that could tell if a patient was suffering from pneumonia or not, in this paper we present a model that distinguishes between a bacterial disease, a viral infection, or a finding caused by COVID-19. The aim of this research is to demonstrate whether pneumonia can be detected or even spatially localized using a uniform, supervised classification.

The critical hypoxia in COVID-19 patients during this pandemic, has taken away many lives all around the globe. The mechanism has been poorly understood and initially, word got around that it was a SARS (Severe Acute Respiratory Syndrome) pneumonia. The atypical images in lung computerized axial tomography (CAT) scans were alarming. This immediately alerted everyone including poor countries to purchase lacking sophisticated ventilator equipment. However, in some countries, even 88% of the patients on ventilators lost their lives. New observations and pathological findings are gradually clarifying the disease. What seems evident is that it is not only one disease but several, with different responses in different countries and different altitudes. The critical hypoxia and «gasping» present in some patients are not totally understood. It was mentioned that it could be like a High-Altitude Pulmonary Edema (HAPE). Hereby, as high-altitude medicine and hypoxia physiology specialists, we compare the pathophysiology with that of high-altitude exposure in order to understand the mechanisms involved. Some differences in lung radiological images along with transmission and viral attack mechanisms are discussed. The oxygen transport triad used at high-altitude can be applied on this pathology in order to propose even the use of erythropoietin (EPO) early in the treatment. The immune system is the most important long-term survival tool, so we suggest a short-term strategy: the use of special Earth open-circuit astronaut-resembling suits with effective outside air filtering re-breathing mechanisms in order to return to work and daily activities, without contamination risk. Thereby, the curve can be flattened without quarantine and the economy could recover.

The current global pandemic of coronavirus disease 2019 (COVID-19) caused by the coronavirus SARS-CoV-2 has already had a major adverse impact on the world due to the exponentially increasing deaths due to the disease and the extreme actions taken by the world community to prevent its spread. It is important to explore novel methods of reducing the illnesses and fatality rates of the coronavirus-infected patients. Since the weakness of the immune system is one of the major contributing factors for the illnesses caused by such viruses, and since inflammation is a major contributing factor for the mortality of COVID-19 patients, interventions that boost the immune system and/or are anti-inflammatory may reduce the COVID-19 incidence and the mortality due to the disease. A large variety of interventions are known to improve the immune response and/or reduce inflammation. However, all the interventions would not be applicable or acceptable to everyone and so the interventions would need to be individualized based on individual circumstances and preferences. This approach, known as “Individualized Interventions to Improve the Immune Response”, or the I⁴R approach, should be studied in pilot clinical trials urgently, in order to potentially reduce the harm caused by the current coronavirus pandemic.

Mankind faces a coronavirus pandemic originating from a seafood market in Wuhan, China since December 2019. The pathogen was named novel coronavirus (n-CoV) and bats are the identified key reservoir. The coronavirus disease 2019 (COVID-19) quickly spread over China across the globe, turned into a pandemic with exponentially increasing numbers of cases and significant mortality rate. China reacted with lockdowns and strict control measurements to prevent spreading the virus. The treatment of severe cases was hampered by lack of specific vaccines. Vaccine-development and production is a painstaking process and can only be enforced by international cooperation. Different supportive treatment options surfaced due to combinations of antiviral agents with antibiotic drugs. Elderly, male, immune-suppressed patients with co-morbidities showed a high mortality rate. Health literacy, strong immune system, adequate serum 25-hydroxyvitamin D (25(OH)D) concentrations and healthy life style choices can support fast recovery. Antibiotic resistance needs to be addressed by development of new generation antimicrobials against nosocomial infections in preparation for future outbreaks. Plant-biosynthesis of nanomaterials and antiseptics may help in prevention and recovery rate. Prevalence of COVID-19 maybe inversely related to BCG vaccination, endemicity of malaria, humidy and temperature but directly with latitude. Recommendations to prevent the spread of COVID-19 should be followed strictly.

Background. Chest CT is widely regarded as a dependable imaging technique for detecting pneumonia in COVID-19 patients, but there is growing interest in microwave radiometry (MWR) of the lungs as a possible substitute for diagnosing lung involvement. Aim. The aim of the study is to examine the utility of the MWR approach as a screening tool for diagnosing pneumonia with complications in patients with COVID-19. Methods. Our study involved two groups of participants. The control group consisted of 50 individuals (24 male and 26 female) between the ages of 20 to 70 years who underwent clinical evaluations and had no known medical conditions. The main group included 142 participants (67 men and 75 women) between the ages of 20 to 87 years who were diagnosed with COVID-19 complicated by pneumonia and were admitted to the emergency department between June 2020 to June 2021. Skin and lung temperatures were measured at 14 points, including 2 additional reference points, using a previously established method. Lung temperature data were obtained with the MWR2020 (RTM-01-RES) (MMWR LTD, Edinburgh, UK), a CE Class I device. All participants underwent clinical evaluations, laboratory tests, chest CT scans, MWR of the lungs, and reverse transcriptase polymerase chain reaction (RT-PCR) testing for SARS-CoV-2. Results. The MWR exhibits a high predictive capacity as demonstrated by its sensitivity of 98.6% and specificity of 84.0%. Conclusions. MWR of the lungs can be a valuable substitute for chest CT in diagnosing pneumonia in patients with COVID-19, especially in situations where chest CT is unavailable or impractical.

As new vaccines reduce P. falciparum (Pf) cases, clinicians can focus on rescuing more children with cerebral malaria (CM). Adjunctive “therapeutically-rational exchange transfusion” (T-REX) refers to using special “Pf-resistant” donor red blood cells (RBCs) that secrete nano-sized RBC extracellular vesicles (EVs). Can some RBC EVs rapidly dislodge Pf-infected RBCs (iRBCs) sequestered in blood vessels and reduce inflammation? Does post-exchange “rebound parasitemia” reflect sequestration-reversal? We reviewed case-reports, EV and liposome studies, expert perspectives, and time-sequence data. In the AQUAMAT study, median coma-recovery time was 20 hours for artesunate. In contrast, a CM patient treated with type-O T-REX quickly began speaking (during the procedure). For other rapid-recovery CM patients, donor RBC variables had not been specified. Despite rapid Pf-killing, drugs need 20 hours to substantially reduce iRBC cytoadhesion while EVs can selectively bind distant inflamed tissues within 15 minutes. RBCs stressed by blood-bank storage and Pf infection secrete EVs. Post-exchange “rebound parasitemia” can occur within 60 minutes and may reflect release of sequestered iRBCs. Sequestration-reversal can be assessed by monitoring Pf parasitemia and total Pf biomass. New data suggest clinicians, working with transfusion- and laboratory-medicine physicians, can, and should, assess T-REX options and publish their findings to help clarify how RBC EVs may serve as therapeutic “decoy ligands.”

A machine learning method for classifying Lung UltraSound is here proposed to pro- vide a point of care tool for supporting a safe, fast and accurate diagnosis, that can also be useful during a pandemic like as SARS-CoV-2. Given the advantages (e.g. safety, rapidity, portability, cost-effectiveness) provided by the ultrasound technology over other methods (e.g. X-ray, computer tomography, magnetic resonance imaging), our method was validated on the largest LUS public dataset. Focusing on both accuracy and efficiency, our solution is based on an efficient adaptive ensembling of two EfficientNet-b0 models reaching 100% of accuracy, which, to our knowledge, outperforms the previous state-of-the-art. The complexity of this solution keeps the number of parameters in the same order as an EfficientNet-b0 by adopting specific design choices that are adaptive ensembling with a combination layer, ensembling performed on the deep features, minimal ensemble only two weak models. Moreover, a visual analysis of the saliency maps on sample images of all the classes of the dataset reveals where the focus is on an inaccurate weak model versus an accurate model.

AI is leveraging all aspects of life. Medical services are not untouched. Especially in the field of medical image processing and diagnosis. Big IT and Biotechnology companies are investing millions of dollars in medical and AI research. The recent outbreak of SARS COV-2 gave us a unique opportunity to study for a non interventional and sustainable AI solution. Lung disease remains a major healthcare challenge with high morbidity and mortality worldwide. The predominant lung disease was lung cancer. Until recently, the world has witnessed the global pandemic of COVID19, the Novel coronavirus outbreak. We have experienced how viral infection of lung and heart claimed thousands of lives worldwide. With the unprecedented advancement of Artificial Intelligence in recent years, Machine learning can be used to easily detect and classify medical imagery. It is much faster and most of the time more accurate than human radiologists. Once implemented, it is more cost-effective and time-saving. In our study, we evaluated the efficacy of Microsoft Cognitive Service to detect and classify COVID19 induced pneumonia from other Viral/Bacterial pneumonia based on X-Ray and CT images. We wanted to assess the implication and accuracy of the Automated ML-based Rapid Application Development (RAD) environment in the field of Medical Image diagnosis. This study will better equip us to respond with an ML-based diagnostic Decision Support System(DSS) for a Pandemic situation like COVID19. After optimization, the trained network achieved 96.8% Average Precision which was implemented as a Web Application for consumption. However, the same trained network did not perform like Web Application when ported to Smartphone for Real-time inference, which was our main interest of study. The authors believe, there is scope for further study on this issue. One of the main goals of this study was to develop and evaluate the performance of AI-powered Smartphone-based Real-time Applications. Facilitating primary diagnostic services in less equipped and understaffed rural healthcare centers of the world with unreliable internet service.

Despite innovative advances in anti-infective therapies and vaccine development technologies, community-acquired pneumonia (CAP) remains the most persistent cause of infection-related mortality globally. Confronting the ongoing threat posed by Streptococcus pneumoniae (the pneumococcus), the most common bacterial cause of CAP, particularly to the non-immune elderly, remains challenging due to the propensity of the elderly to develop invasive pneumococcal disease (IPD), together with the predilection of the pathogen for the heart. The resultant development of often fatal cardiovascular events (CVEs), particularly during the first seven days of acute infection, is now recognized as a relatively common complication of IPD. The current review represents an update on the prevalence and types of CVEs associated with acute bacterial CAP, particularly IPD. In addition, it is focused on recent insights into the involvement of the pneumococcal pore-forming toxin, pneumolysin (Ply), in subverting host immune defenses, particularly the protective functions of the alveolar macrophage during early-stage disease. This, in turn, enables extra-pulmonary dissemination of the pathogen, leading to cardiac invasion, cardiotoxicity and myocardial dysfunction. The review concludes with an overview of the current status of macrolide antibiotics in the treatment of bacterial CAP in general, as well as severe pneumococcal CAP, including a consideration of the mechanisms by which these agents inhibit the production of Ply by macrolide-resistant strains of the pathogen.

Malaria is a prevalent disease in several tropical and subtropical regions, including Brazil, where remains a significant public health concern. Despite control efforts, reintroduction of endemics in areas without cases for decades poses a challenge. To assess factors influencing ma-laria risk, regional outbreak cluster analysis and a spatio-temporal models were developed for the Brazilian Amazon, incorporating climate, land use/cover interactions, endemic bird, and amphibian richness. Results showed that amphibian, bird richness and endemism correlated with a reduction in malaria risk. Presence of forest had a positive effect on risk, but it depended on its juxtaposition with anthropic land uses. Biodiversity and landscape composition, rather than forest formation presence alone, modulated malaria risk in the period. Areas with low en-demic species diversity and high human activity, predominantly anthropogenic landscapes posed high malaria risk. This study underscores the importance of considering the broader eco-logical context in malaria control efforts.

The lung microbiota is a complex community of microorganisms that colonize the respiratory tract of individuals from or even before birth. Although the lungs were traditionally believed to be sterile, recent research has shown that there is a diversity of bacterial species in the respiratory system. Knowledge about the lung microbiota in the newborn and its relationship with bacterial infections is of vital importance to understand the pathogenesis of respiratory diseases in neona-tal patients undergoing mechanical ventilation. In this article, the current evidence on the compo-sition of the lung microbiota in the newborn will be reviewed, as well as its role in the develop-ment of bacterial infections in mechanically ventilated neonates. Although advances in many as-pects of the neonatal intensive care unit care have significantly improved the survival of preterm infants, the diagnosis and treatment of ventilator-associated pneumonia has not progressed in recent decades. Avoiding dysbiosis caused by inappropriate use of antibiotics around birth, as well as avoiding intubation of patients or promoting early removal of endotracheal tubes are among the most important preventive measures for ventilator-associated pneumonia. The use of probiotics and prebiotics to prevent infectious, allergic or metabolic complications in the short or long term constitutes a very important field of research in perinatal medicine.

COVID-19 was an inflammatory pneumonia caused by a respiratory infection with a coronavirus named SARS-CoV-2. Severely ill COVID-19 patients could die of acute pulmonary and systemic inflammation. Thus, there was a theory that long COVID-19 shared many similarities with systemic autoimmune diseases. There was also a theory that the SARS-CoV-2 virus could infect many cell- and tissue-types distributed throughout multiple organ systems of the body. I aim to review the above theories using unbiased high-throughput datasets cataloguing gene expression. Studies reviewed used the technology of next generation sequencing, either as bulk tissue RNA sequencing, or as single-cell RNAs sequencing; ingenious methods for signal deconvolution were then used to identify individual cell types. Datasets reviewed suggested that severe COVID-19 induced expression of genes associated with pro-inflammatory signaling, tissue development or remodeling, scarring, or cell death. The datasets also provided evidence for several inflammatory syndromes associated with COVID-19, such as neuronal COVID, acute respiratory disease syndrome, vascular inflammation, or multisystem inflammatory syndrome. Indeed, inflammatory signal during severe COVID-19 was reported in many cell types, for example in structural cells, in infiltrating immune cells, in the vascular system, or in circulating cells in the blood. There was also frequently a change in proportions of immune cell-types in the blood, epithelial cells in the lungs, or among infiltrating immune cells.

Inflammation involves the activation of innate immune cells and is believed to play an important role in the development and progression of both infectious and non-infectious diseases such as neurodegeneration, rheumatoid arthritis or cancer. Inflammation in the brain is marked by the upregulation of the translocator protein (TSPO) in microglia. Moreover, high TSPO levels are found, for example in macrophages during rheumatoid arthritis and in malignant tumor cells compared to its relatively low physiological expression. The same applies for cycloxygenase-2 (COX-2), which is constitutively expressed in the kidney, brain, thymus and gastrointestinal tract, but induced in microglia, macrophages and synoviocytes during inflammation. This puts TSPO and COX-2 in the spotlight as important targets for the diagnosis of inflammation. Imaging modalities, such as positron emission tomography and single-photon emission tomography, can be used to localize inflammatory processes and to track their progression over time. They could also enable to monitor the efficacy of therapy and predict its outcome. This review focuses on the current development of PET and SPECT tracers not only for the detection of neuroinflammation, but also for emerging diagnostic measures in infectious and other non-infectious diseases like rheumatic arthritis, cancer, cardiac inflammation and in lung diseases.

This overview initially describes insect immune reactions and then brings together present knowledge of the interactions of vector insects with their invading parasites and pathogens. It is a way of introducing this special issue with subsequent papers presenting the latest details of these interactions in each particular group of vectors. Hopefully, this paper will fill a void in the literature since brief descriptions of vector immunity have now been brought together in one publication and could form a starting point for those interested and new to this important area. Descriptions are given on the immune reactions of mosquitoes, blackflies, sandflies, tsetse flies, lice, fleas and triatomine bugs. Cellular and humoral defences are described separately but emphasis is made on the co-operation of these processes in the completed immune response. The paper also emphasises the need of great care in extracting haemocytes for subsequent study as appreciation of their fragile nature is sometimes overlooked with non-sterile media, smearing techniques and excessive centrifugation sometimes used. The potential vital role of eicosanoids in the instigation of many of the immune reactions described is also discussed. Finally, the priming of the immune system, mainly in mosquitoes, is considered and one possible mechanism is presented

Number of studies claim that tobacco control (TC) regulations are associated with reductions in smoking-related hospitalisation rates, however very few have estimated the impact of TC laws (TCL) at both countrywide and regional levels, and none of them - in relation to compliance with TC regulations. This study evaluates the effects of Russian TCL on hospital admission (HA) rates for pneumonia countrywide and in 10 Russian regions and the extent of these effects in connection with the compliance to TCL. Methods: HA rates for pneumonia during 2005–2019 were analysed to compare the periods before and after the adoption of TCL in 2013. An interrupted time series design and a Poisson regression model were used to estimate the immediate and long-term effects of TCL on pneumonia annual hospitalisation rates after the TCL adoption, compared with the pre-law period. The 10 Russian regions were compared using the TCL Implementation Scale (TCIS) developed on the basis of the results of Russian TC policy evaluation survey; Spearman’s rank correlation and linear regression models were employed. Results showed a 14.3% reduction in HA rates for pneumonia (RR 0.88; p=0.01) after the adoption of TCL in Russia with significant long-term effect after 2013 (RR 0.86; p=0.006). Regions with better enforcement of TCL exhibited greater reductions in pneumonia HA rates (rsp=−0.55; p=0.04); (=−4.21; p=0.02). Conclusions: TCL resulted in a sustained reduction in pneumonia hospitalisation rates, but these effects, varying by region, may depend on the scale of the TCL enforcement.

The world is in the grips of the COVID-19 pandemic. Public health measures that can reduce the risk of infection and death in addition to quarantines are desperately needed. This article reviews the roles of vitamin D in reducing risk of respiratory tract infections, knowledge about the epidemiology of influenza and COVID-19, and how vitamin D supplementation might be a useful measure to reduce risk. Through several mechanisms, vitamin D can reduce risk of infections. Those mechanisms include inducing cathelicidins and defensins that can lower viral replication rates and reducing concentrations of pro-inflammatory cytokines that produce the inflammation that injures the lining of the lungs, leading to pneumonia, as well as increase concentrations of anti-inflammatory cytokines. Several observational studies and clinical trials reported that vitamin D supplementation reduced risk of influenza, whereas others did not. Evidence supporting the role of vitamin D in reducing risk of COVID-19 includes that the outbreak occurred in winter, a time when 25-hydroxyvitamin D [25(OH)D] concentrations are lowest; that the number of cases in the Southern Hemisphere near the end of summer are low; that vitamin D deficiency has been found to contribute to acute respiratory distress syndrome, and that case-fatality rates increase with age and with chronic disease comorbidity, both of which are associated with lower 25(OH)D concentration. To reduce risk of infection, it is recommended that people at risk of influenza and/or COVID-19 consider taking 10,000 IU/d of vitamin D₃ for a few weeks to rapidly raise 25(OH)D concentrations, followed by 5000 IU/d. The goal should be to raise 25(OH)D concentrations above 40–60 ng/ml (100–150 nmol/l). For treatment of people who become infected with COVID-19, higher vitamin D₃ doses might be useful. Randomized controlled trials and large population studies should be conducted to evaluate these recommendations.

At the end of 2019, while the world was being hit by the COVID-19 virus and, consequently, was living a global health crisis, many other pandemics were putting humankind in danger. The role of social media is of paramount importance in these kinds of contexts since they help health systems to cope with emergencies by contributing to conducting some activities such as the identification of public concerns, the detection of infections’ symptoms, and the traceability of the virus diffusion. In this paper, we have analyzed comments on events related to cholera, ebola, HIV/AIDS, influenza, malaria, Spanish influenza, swine flu, tuberculosis, typhus, yellow fever, and zika, collecting 369,472 tweets from the 3rd of March to the 15th of September, 2022. Our analysis has started with the collection of comments composed of unstructured texts on which we have applied natural language processing solutions. Afterward, we have employed topic modelling and sentiment analysis techniques to obtain a collection of people’s concerns and attitudes toward these pandemics. According to our findings, people's discussions were mostly about malaria, influenza, and tuberculosis and the focus was on the diseases themselves. As regards emotions, the most popular were fear, trust, and disgust where trust is mainly regarding HIV/AIDS tweets.

Advances in biological sciences have been applied in medicine, agriculture and industry with great benefit. Some recent trends in society, governance structures and communications, however, appear to be hampering the use of new scientific findings for controlling infectious diseases. These limitations are illustrated with examples related to (i) the adaptation of fresh water mosquito vectors of major arboviral diseases to salinity in coastal areas with consequences for disease transmission, (ii) understanding the implications of reduced dengue transmission during the COVID-19 lockdown for dengue control, (iii) causes underlying the rapid spread of the malaria vector Anopheles stephensi in South Asia and Africa, (iv) the application of serodiagnostic techniques for Lyme disease and tick-borne relapsing fever caused by tick-borne bacteria of the genus Borrelia, and (v) COVID-19 prevention.