-
Emerging Infectious Diseases Nov 2023Melioidosis, caused by the environmental gram-negative bacterium Burkholderia pseudomallei, usually develops in adults with predisposing conditions and in Australia more... (Review)
Review
Melioidosis, caused by the environmental gram-negative bacterium Burkholderia pseudomallei, usually develops in adults with predisposing conditions and in Australia more commonly occurs during the monsoonal wet season. We report an outbreak of 7 cases of melioidosis in immunocompetent children in Australia. All the children had participated in a single-day sporting event during the dry season in a tropical region of Australia, and all had limited cutaneous disease. All case-patients had an adverse reaction to oral trimethoprim/sulfamethoxazole treatment, necessitating its discontinuation. We describe the clinical features, environmental sampling, genomic epidemiologic investigation, and public health response to the outbreak. Management of this outbreak shows the potential benefits of making melioidosis a notifiable disease. The approach used could also be used as a framework for similar outbreaks in the future.
Topics: Adult; Humans; Child; Melioidosis; Burkholderia pseudomallei; Australia; Genomics; Disease Outbreaks
PubMed: 37877500
DOI: 10.3201/eid2911.230951 -
Value in Health : the Journal of the... Jan 2024The COVID-19 pandemic placed significant strain on many health systems and economies. Mitigation policies decreased health impacts but had major macroeconomic impact.... (Review)
Review
OBJECTIVES
The COVID-19 pandemic placed significant strain on many health systems and economies. Mitigation policies decreased health impacts but had major macroeconomic impact. This article reviews models combining epidemiological and macroeconomic projections to enable policy makers to consider both macroeconomic and health objectives.
METHODS
A scoping review of epidemiological-macroeconomic models of COVID-19 was conducted, covering preprints, working articles, and journal publications. We assessed model methodologies, scope, and application to empirical data.
RESULTS
We found 80 articles modeling both the epidemiological and macroeconomic outcomes of COVID-19. Model scope is often limited to the impact of lockdown on health and total gross domestic product or aggregate consumption and to high-income countries. Just 14% of models assess disparities or poverty. Most models fall under 4 categories: compartmental-utility-maximization models, epidemiological models with stylized macroeconomic projections, epidemiological models linked to computable general equilibrium or input-output models, and epidemiological-economic agent-based models. We propose a taxonomy comparing these approaches to guide future model development.
CONCLUSIONS
The epidemiological-macroeconomic models of COVID-19 identified have varying complexity and meet different modeling needs. Priorities for future modeling include increasing developing country applications, assessing disparities and poverty, and estimating of long-run impacts. This may require better integration between epidemiologists and economists.
Topics: Humans; COVID-19; Pandemics; Communicable Disease Control; Models, Economic; Poverty
PubMed: 37913921
DOI: 10.1016/j.jval.2023.10.008 -
World Journal of Gastroenterology Aug 2023One of the most prevalent malignancies in the world is esophageal cancer (EC). The 5-year survival rate of EC remains pitiful despite treatment advancements. Neoadjuvant... (Review)
Review
One of the most prevalent malignancies in the world is esophageal cancer (EC). The 5-year survival rate of EC remains pitiful despite treatment advancements. Neoadjuvant chemoradiotherapy in conjunction with esophagectomy is the standard of care for patients with resectable disease. The pathological complete response rate, however, is not acceptable. A distant metastasis or a locoregional recurrence will occur in about half of the patients. To increase the clinical effectiveness of therapy, it is consequently vital to investigate cutting-edge and potent therapeutic modalities. The approach to the management of resectable EC using immunotherapy has been considerably altered by immune checkpoint inhibitors. Systemic immunotherapy has recently been shown to have the potential to increase the survival of patients with resectable EC, according to growing clinical data. A combination of chemotherapy, radiation, and immunotherapy may have a synergistic antitumor impact because, according to mounting evidence, these treatments can stimulate the immune system a number of different pathways. In light of this, it makes sense to consider the value of neoadjuvant immunotherapy for patients with surgically treatable EC. In this review, we clarify the rationale for neoadjuvant immunotherapy in resectable EC patients, recap the clinical outcomes of these approaches, go through the upcoming and ongoing investigations, and emphasize the difficulties and unmet research requirements.
Topics: Humans; Esophageal Neoplasms; Esophagectomy; Immunotherapy; Neoadjuvant Therapy
PubMed: 37662861
DOI: 10.3748/wjg.v29.i30.4628 -
Nature Communications Nov 2023The leishmanin skin test was used for almost a century to detect exposure and immunity to Leishmania, the causative agent of leishmaniasis, a major neglected tropical...
The leishmanin skin test was used for almost a century to detect exposure and immunity to Leishmania, the causative agent of leishmaniasis, a major neglected tropical disease. Due to a lack of antigen used for the intradermal injection, the leishmanin skin test is no longer available. As leishmaniasis control programs are advancing and new vaccines are entering clinical trials, it is essential to re-introduce the leishmanin skin test. Here we establish a Leishmania donovani strain and describe the production, under Good Laboratory Practice conditions, of leishmanin soluble antigen used to induce the leishmanin skin test in animal models of infection and vaccination. Using a mouse model of cutaneous leishmaniasis and a hamster model of visceral leishmaniasis, soluble antigen induces a leishmanin skin test response following infection and vaccination with live attenuated Leishmania major (LmCen). Both the CD4 and CD8 T-cells are necessary for the leishmanin skin test response. This study demonstrates the feasibility of large-scale production of leishmanin antigen addressing a major bottleneck for performing the leishmanin skin test in future surveillance and vaccine clinical trials.
Topics: Animals; Leishmania donovani; CD8-Positive T-Lymphocytes; Antigens, Protozoan; Leishmaniasis, Cutaneous; Skin Tests
PubMed: 37919280
DOI: 10.1038/s41467-023-42732-2 -
BMJ Open Jun 2023Malaria infection and curable sexually transmitted infections and reproductive tract infections (STIs/RTIs) adversely impact pregnancy outcomes. In sub-Saharan Africa,...
Coinfections of malaria and sexually transmitted and reproductive tract infections in pregnancy in sub-Saharan Africa: a systematic review and individual participant data meta-analysis protocol.
INTRODUCTION
Malaria infection and curable sexually transmitted infections and reproductive tract infections (STIs/RTIs) adversely impact pregnancy outcomes. In sub-Saharan Africa, the prevalence of malaria and curable STIs/RTIs is high and, where coinfection is common, combination interventions may be needed to improve pregnancy outcomes. The aim of this systematic review is to estimate the prevalence of malaria and curable STI/RTI coinfection during pregnancy, risk factors for coinfection and prevalence of associated adverse pregnancy outcomes.
METHODS AND ANALYSIS
We will use three electronic databases, PubMed, EMBASE and Malaria in Pregnancy Library to identify studies involving pregnant women attending routine antenatal care facilities in sub-Saharan Africa and reporting malaria and curable STI/RTI test results, published in any language since 2000. We will search databases in the second quarter of 2023 and repeat the search before completion of our analyses. The first two authors will screen titles and abstracts, selecting studies that meet inclusion criteria and qualify for full-text screening. If agreement on inclusion/exclusion cannot be reached, the last author will serve as arbiter. We will extract data from eligible publications for a study-level meta-analysis. We will contact research groups of included studies and request individual participant data for meta-analysis. The first two authors will conduct a quality appraisal of included studies using the GRADE system. The last author will adjudicate if the first two authors do not agree on any appraisals. We will conduct sensitivity analyses to test the robustness of effect estimates over time (by decade and half-decade periods), geography (East/Southern Africa vs West/Central Africa), gravidity (primigravidae, secundigravidae, multigravidae), treatment type and dosing frequency, and malaria transmission intensity.
ETHICS AND DISSEMINATION
We obtained ethics approval from the London School of Hygiene & Tropical Medicine (LSHTM Ethics Ref: 26167). Results of this study will be disseminated via peer-reviewed publication and presentation at scientific conferences.
PROSPERO REGISTRATION NUMBER
CRD42021224294.
Topics: Humans; Female; Pregnancy; Reproductive Tract Infections; Coinfection; Sexually Transmitted Diseases; Malaria; Pregnancy Outcome; Africa South of the Sahara; Systematic Reviews as Topic; Meta-Analysis as Topic
PubMed: 37339835
DOI: 10.1136/bmjopen-2023-074896 -
IScience Jul 2023Maternal colonization by Group B Streptococcus (GBS) can lead to severe infection in neonates and has also been associated with prematurity and stillbirth. Better...
Maternal colonization by Group B Streptococcus (GBS) can lead to severe infection in neonates and has also been associated with prematurity and stillbirth. Better quantitative understanding of the trajectories of GBS carriage during pregnancy is essential for the design of informative epidemiological studies. Here, we describe analyses of published longitudinal data using Bayesian hidden Markov models, which involve the estimation of parameters related to the succession of latent states (infection status) and observations (culture positivity). In addition to quantifying infection acquisition and clearance probabilities, the statistical approach also suggests that for some longitudinal patterns of culture results, pregnant women were likely to have been GBS-colonized despite a negative diagnostic result. We believe this method, if used in future longitudinal studies of maternal GBS colonization, would improve our understanding of the pathologies linked to this bacterium and could also inform maternal GBS vaccine trial design.
PubMed: 37534153
DOI: 10.1016/j.isci.2023.107023 -
Experimental & Molecular Medicine Apr 2024
Topics: Humans; Genome; Animals; Cell Nucleus
PubMed: 38658700
DOI: 10.1038/s12276-024-01248-5 -
Biomedicine & Pharmacotherapy =... Sep 2023The manipulation of macrophage recruitment and their shift in the M1/M2 ratio is a promising approach to mitigate osteoarthritis (OA). Nevertheless, the current clinical...
AIMS
The manipulation of macrophage recruitment and their shift in the M1/M2 ratio is a promising approach to mitigate osteoarthritis (OA). Nevertheless, the current clinical medication available for OA is only palliative and may result in undesirable outcomes. Hence, it is urgent to explore alternative disease-modifying drug supplement that are both safer and more effective in OA treatment, like probiotic and probiotic-derived membrane vesicles.
METHODS
The synovial inflammation and cartilage damage in collagenase-induced OA (CIOA) mice were observed using haematoxylin and eosin, saffron O-solid green and immunohistochemical staining. Bipedal balance test and open field test were conducted to determine the effectiveness of L. johnsonii-derived membrane vesicles (LJ-MVs) in reducing joint pain of CIOA mice. Additionally, Transwell, western blot, and immunological testing were used to examine the effect of LJ-MVs on macrophage migration and reprogramming. Furthermore, a 4D label-free proteomic analysis of LJ-MVs and their parent bacterium was performed, and the glutamine synthetase (GS)/mTORC1 axis in macrophage was verified by western blot.
RESULTS
L. johnsonii and its membrane vesicles, LJ-MVs, exhibit a novel ability to mitigate inflammation, cartilage damage, and pain associated with OA. This is achieved by their ability to impede macrophage migration, M1-like polarization, and inflammatory mediators secretion, while simultaneously promoting the M2/M1 ratio in synovial macrophages. The mechanism underlying this effect involves the modulation of macrophage GS/mTORC1 pathway, at least partially.
SIGNIFICANCE
Owing to their probiotic derivation, LJ-MVs will be a more dependable and potent disease-modifying drugs for the prevention and therapy of OA in the long run.
Topics: Mice; Animals; Lactobacillus johnsonii; Glutamate-Ammonia Ligase; Synovial Membrane; Mechanistic Target of Rapamycin Complex 1; Proteomics; Osteoarthritis; Macrophages; Inflammation
PubMed: 37499456
DOI: 10.1016/j.biopha.2023.115204 -
Infectious Diseases of Poverty May 2024Lao PDR has made significant progress in malaria control. The National Strategic Plans outline ambitious targets, aiming for the elimination of Plasmodium falciparum and... (Review)
Review
BACKGROUND
Lao PDR has made significant progress in malaria control. The National Strategic Plans outline ambitious targets, aiming for the elimination of Plasmodium falciparum and P. vivax malaria from all northern provinces by 2025 and national elimination by 2030. This article presents an overview of malaria epidemiology, surveillance, and response systems in Lao PDR, emphasizing experiences and achievements in transmission reduction.
METHODS
Data on surveillance, monitoring and evaluation systems, human resources, infrastructure, and community malaria knowledge during 2010-2020 were systematically gathered from the national program and relevant documents. The collected information was synthesized, and discussions on challenges and future prospects were provided.
RESULTS
Malaria control and elimination activities in Lao PDR were implemented at various levels, with a focus on health facility catchment areas. There has been significant progress in reducing malaria transmission throughout the country. Targeted interventions, such as case management, vector control, and community engagement, using stratification of control interventions by catchment areas have contributed to the decline in malaria cases. In elimination areas, active surveillance strategies, including case and foci investigation, are implemented to identify and stop transmission. The surveillance system has facilitated timely detection and response to malaria cases, enabling these targeted interventions in higher-risk areas.
CONCLUSIONS
The malaria surveillance and response system in Lao PDR has played a crucial role in reducing transmission and advancing the country towards elimination. Challenges such as importation, drug resistance, and sustaining support require ongoing efforts. Further strengthening surveillance, improving access to services, and addressing transmission determinants are key areas of focus to achieve malaria elimination and enhance population health in Lao PDR.
Topics: Laos; Humans; Disease Eradication; Malaria; Epidemiological Monitoring; Malaria, Vivax; Population Surveillance; Malaria, Falciparum
PubMed: 38783374
DOI: 10.1186/s40249-024-01202-7 -
World Journal of Gastrointestinal... Jun 2023Biliary tract cancers (BTC) are frequently identified at late stages and have a poor prognosis due to limited systemic treatment regimens. For more than a decade, the... (Review)
Review
Biliary tract cancers (BTC) are frequently identified at late stages and have a poor prognosis due to limited systemic treatment regimens. For more than a decade, the combination of gemcitabine and cis-platin has served as the first-line standard treatment. There are few choices for second-line chemo-therapy. Targeted treatment with fibroblast growth factor receptor 2 inhibitors, neurotrophic tyrosine receptor kinase inhibitors, and isocitrate dehydrogenase 1 inhibitors has had important results. Immune checkpoint inhibitors (ICI) such as pembrolizumab are only used in first-line treatment for microsatellite instability high patients. The TOPAZ-1 trial's outcome is encouraging, and there are several trials underway that might soon put targeted treatment and ICI combos into first-line options. Newer targets and agents for existing goals are being studied, which may represent a paradigm shift in BTC management. Due to a scarcity of targetable mutations and the higher toxicity profile of the current medications, the new category of drugs may occupy a significant role in BTC therapies.
PubMed: 37389105
DOI: 10.4251/wjgo.v15.i6.959