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Conflict and Health Apr 2024Conflict situations, armed or not, have been associated with emergence and transmission of infectious diseases. This review aims to identify the pathways through which... (Review)
Review
BACKGROUND
Conflict situations, armed or not, have been associated with emergence and transmission of infectious diseases. This review aims to identify the pathways through which infectious diseases emerge within conflict situations and to outline appropriate infectious disease preparedness and response strategies.
METHODS
A systematic review was performed representing published evidence from January 2000 to October 2023. Ovid Medline and Embase were utilised to obtain literature on infectious diseases in any conflict settings. The systematic review adhered to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analysis). No geographical restrictions were imposed.
FINDINGS
Our review identified 51 studies covering AIDS, Hepatitis B, Tuberculosis, Cholera, Coronavirus 2, Ebola, Poliomyelitis, Malaria, Leishmaniasis, Measles, Diphtheria, Dengue and Acute Bacterial Meningitis within conflict settings in Europe, Middle East, Asia, and Africa since October 2023. Key factors contributing to disease emergence and transmission in conflict situations included population displacement, destruction of vital infrastructure, reduction in functioning healthcare systems and healthcare personnel, disruption of disease control programmes (including reduced surveillance, diagnostic delays, and interrupted vaccinations), reduced access by healthcare providers to populations within areas of active conflict, increased population vulnerability due to limited access to healthcare services, and disruptions in the supply chain of safe water, food, and medication. To mitigate these infectious disease risks reported preparedness and response strategies included both disease-specific intervention strategies as well as broader concepts such as the education of conflict-affected populations through infectious disease awareness programmes, investing in and enabling health care in locations with displaced populations, intensifying immunisation campaigns, and ensuring political commitment and intersectoral collaborations between governments and international organisations.
CONCLUSION
Conflict plays a direct and indirect role in the transmission and propagation of infectious diseases. The findings from this review can assist decision-makers in the development of evidence-based preparedness and response strategies for the timely and effective containment of infectious disease outbreaks in conflict zones and amongst conflict-driven displaced populations.
FUNDING
European Centre for Disease Prevention and Control under specific contract No. 22 ECD.13,154 within Framework contract ECDC/2019/001 Lot 1B.
PubMed: 38584269
DOI: 10.1186/s13031-023-00568-z -
Biomolecules Jul 2023Poly(ADP-ribose) (PAR) Polymerase 1 (PARP-1), also known as ADP-ribosyl transferase with diphtheria toxin homology 1 (ARTD-1), is a critical player in DNA damage repair,... (Review)
Review
Poly(ADP-ribose) (PAR) Polymerase 1 (PARP-1), also known as ADP-ribosyl transferase with diphtheria toxin homology 1 (ARTD-1), is a critical player in DNA damage repair, during which it catalyzes the ADP ribosylation of self and target enzymes. While the nuclear localization of PARP-1 has been well established, recent studies also suggest its mitochondrial localization. In this review, we summarize the differences between mitochondrial and nuclear Base Excision Repair (BER) pathways, the involvement of PARP-1 in mitochondrial and nuclear BER, and its functional interplay with other BER enzymes.
Topics: Poly(ADP-ribose) Polymerase Inhibitors; DNA Repair; Mitochondria; Poly Adenosine Diphosphate Ribose
PubMed: 37627260
DOI: 10.3390/biom13081195 -
Neuro-oncology Oct 2023Glioblastoma is a deadly brain tumor without any significantly successful treatments to date. Tumor antigen-targeted immunotherapy platforms including peptide and... (Review)
Review
Glioblastoma is a deadly brain tumor without any significantly successful treatments to date. Tumor antigen-targeted immunotherapy platforms including peptide and dendritic cell (DC) vaccines, have extended survival in hematologic malignancies. The relatively "cold" tumor immune microenvironment and heterogenous nature of glioblastoma have proven to be major limitations to translational application and efficacy of DC vaccines. Furthermore, many DC vaccine trials in glioblastoma are difficult to interpret due to a lack of contemporaneous controls, absence of any control comparison, or inconsistent patient populations. Here we review glioblastoma immunobiology aspects that are relevant to DC vaccines, review the clinical experience with DC vaccines targeting glioblastoma, discuss challenges in clinical trial design, and summarize conclusions and directions for future research for the development of effective DC vaccines for patients.
Topics: Humans; Glioblastoma; Cancer Vaccines; Dendritic Cells; Glioma; Brain Neoplasms; Immunotherapy; Tumor Microenvironment
PubMed: 37289203
DOI: 10.1093/neuonc/noad088 -
Haematologica Jan 2024Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy that presents with characteristic dark purple skin papules, plaques, and tumors,... (Review)
Review
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy that presents with characteristic dark purple skin papules, plaques, and tumors, but may also involve the bone marrow, blood, lymph nodes, and central nervous system. The disease, which commonly affects older men but can also present in children, is associated with a distinct immunophenotype including universal expression of CD123, the α chain of the interleukin 3 receptor. Recently, tagraxofusp, a CD123-targeting drug consisting of the ligand for CD123, interleukin 3, conjugated to a truncated diphtheria toxin payload was approved for treatment of BPDCN. This was the first agent specifically approved for BPDCN and the first CD123 targeted agent in oncology. Here, we review the development of tagraxofusp, and the key preclinical insights and clinical data that led to approval. Tagraxofusp treatment is associated with a unique toxicity, capillary leak syndrome (CLS), which can be severe but is manageable with proper patient selection and monitoring, early recognition, and directed intervention. We outline our approach to the use of tagraxofusp and discuss open questions in the treatment of BPDCN. Overall, tagraxofusp represents a unique targeted therapy and a step forward in meeting an unmet need for patients with this rare disease.
Topics: Male; Child; Humans; Aged; Interleukin-3 Receptor alpha Subunit; Dendritic Cells; Hematologic Neoplasms; Recombinant Fusion Proteins; Acute Disease; Myeloproliferative Disorders; Skin Neoplasms
PubMed: 36951152
DOI: 10.3324/haematol.2022.282171 -
Human Vaccines & Immunotherapeutics Aug 2023A growing literature supports a protective association between vaccines targeting an array of pathogens (e.g., influenza, pneumococcus, herpes zoster) and the risk of...
A growing literature supports a protective association between vaccines targeting an array of pathogens (e.g., influenza, pneumococcus, herpes zoster) and the risk of Alzheimer disease (AD). This article discusses the potential underlying mechanisms for this apparent protective effect of immunizations against infectious pathogens on the risk of AD; explores the basic and pharmacoepidemiologic evidence for this association, with particular attention paid to important methodological variations among the epidemiologic studies; and reviews the remaining uncertainties regarding the effects of anti-pathogen vaccines on Alzheimer disease and all-cause dementia, with recommendations for future directions to address those uncertainties.
Topics: Humans; Alzheimer Disease; Vaccination; Influenza Vaccines; Immunization; Influenza, Human; Diphtheria-Tetanus-acellular Pertussis Vaccines
PubMed: 37291109
DOI: 10.1080/21645515.2023.2216625 -
Disaster after disaster: the outbreak of infectious diseases in Pakistan in the wake of 2022 floods.Annals of Medicine and Surgery (2012) Feb 2024In June 2022, Pakistan witnessed catastrophic floods, affecting millions of people. The ensuing epidemics of cholera, cryptosporidiosis, rotavirus infections,... (Review)
Review
In June 2022, Pakistan witnessed catastrophic floods, affecting millions of people. The ensuing epidemics of cholera, cryptosporidiosis, rotavirus infections, generalized diarrhoea, typhoid and paratyphoid fevers, as well as the frequency of vector-borne diseases including malaria and dengue fever, are studied in this investigation. It also explores the latest outbreak of poliomyelitis and the frequency of respiratory diseases such COVID-19, diphtheria, and tuberculosis, as well as how floods have contributed to skin and eye problems. The report also describes the obstacles governments must overcome in order to manage these health emergencies and offers possible solutions for reducing the effects of ongoing and anticipated epidemics. This flood emphasizes the pressing need for international action and acts as an alarming indicator of the significant impact of climate change. It emphasizes how crucial it is to have effective flood response and preparation strategies in developing nations that are vulnerable to natural disasters.
PubMed: 38333326
DOI: 10.1097/MS9.0000000000001597 -
Pakistan Journal of Medical Sciences Jan 2024Diphtheria vaccination in the EPI program has controlled much of the childhood infection. Nevertheless, sporadic adult cases of Diphtheria come up every now and then in...
Diphtheria vaccination in the EPI program has controlled much of the childhood infection. Nevertheless, sporadic adult cases of Diphtheria come up every now and then in Pakistan and other South-Asian countries. This is, most likely, due to the lack of booster dosing of Diphtheria vaccine in adulthood. In an effort to suppress the spread of this infection, adult vaccinations need to be mandated.
PubMed: 38328652
DOI: 10.12669/pjms.40.2(ICON).8954 -
Indian Journal of Pathology &... Apr 2024Diphtheria is an infectious disease caused by gram-positive bacilli C. diphtheriae involving nasal, pharyngeal, tonsillar, or laryngeal mucus membranes. The mortality...
INTRODUCTION
Diphtheria is an infectious disease caused by gram-positive bacilli C. diphtheriae involving nasal, pharyngeal, tonsillar, or laryngeal mucus membranes. The mortality rate is as high as 20%, with India contributing almost 78% of the world incidence.
AIMS AND OBJECTIVES
We report a fatal case of nasopharyngeal diphtheria with carrier study in close contacts.
MATERIALS AND METHODS
Seven years child presented with fever, throat pain, and earache for 3 days followed by neck swelling and noisy respiration. On examination, membrane was present in the throat, which was received for Albert and Gram staining and reported as positive for C. diphtheria like organisms followed by culture. The patient was treated with ADS and antibiotics, and intensively managed, but still succumbed to death. Follow-up was done for carriage of C. diphtheriae on the throat and nasopharyngeal swabs of siblings and close contacts. It was isolated in 3 of them. Samples were processed for Gram, Albert stain, and culture. Identification, antibiotic sensitivity, and toxigenicity were done.
RESULTS AND DISCUSSION
Four samples, one from the patient and three from contacts showed the presence of gram-positive slender bacilli with cuneiform arrangement, less cellular infiltrate on the Gram stain, and the presence of few metachromatic granules in the Albert stain. C. diphtheriae was grown on Potassium Tellurite agar. Antibiogram of all isolates was similar with resistance to Erythromycin and sensitivity to Penicillin. Isolates were confirmed by PCR and ToxA gene was detected. Contacts were treated with Penicillin and repeat swabs were negative.
CONCLUSION
Present health statistics and this study suggests, fight against diphtheria in India is far from being over. It still lurks in some remote areas. It is a need to remain vigilant, keep tracing, and treating contacts to curtail down the rate of infection. In view of the resurgence, Government has given directives to replace TT with Td in UIP. Still, a lot needs to be done.
Topics: Child; Humans; Anti-Bacterial Agents; Carrier State; Corynebacterium diphtheriae; Diphtheria; Fatal Outcome; India; Microbial Sensitivity Tests; Nasopharynx; Pharynx
PubMed: 38394413
DOI: 10.4103/ijpm.ijpm_265_23 -
Microorganisms Apr 2024(1) Background: We aim to systematically review the current evidence on immunity against tetanus, diphtheria, and pertussis in adult solid organ transplantation (SOT)... (Review)
Review
(1) Background: We aim to systematically review the current evidence on immunity against tetanus, diphtheria, and pertussis in adult solid organ transplantation (SOT) recipients, either through natural infection or vaccination. (2) Methods: This systematic review was conducted per PRISMA guidelines. We assessed the risk of bias using the Cochrane RoB 2 and ROBINS-I and summarized the findings narratively due to the heterogeneity of the studies. (3) Results: Of the 315 screened articles, 11 were included. Tetanus immunity varied between 55% and 86%, diphtheria immunity from 23% to 75%, and pertussis immunity was between 46% and 82%. Post-vaccination immunity showed variation across the studies, with some indicating reductions and others no change, with antibody responses influenced by transplanted organs, gender, age, and immunosuppressive regimens. The single randomized study exhibited a low risk of bias, while of the ten non-randomized studies, six showed moderate and four serious risks of bias, necessitating cautious interpretation of results. (4) Conclusions: SOT recipients exhibit considerable immunity against tetanus and diphtheria at transplantation, but this immunity decreases over time. Although vaccination can enhance this immunity, the response may be suboptimal, and the increased antibody levels may not persist, underscoring the need for tailored vaccination strategies in this vulnerable population.
PubMed: 38792678
DOI: 10.3390/microorganisms12050847 -
Journal of Neurology Oct 2023Few studies documented the potential association between vaccination and the risk of central demyelination (CD). Specifically, anti-hepatitis B and anti-human...
BACKGROUND
Few studies documented the potential association between vaccination and the risk of central demyelination (CD). Specifically, anti-hepatitis B and anti-human papillomavirus (HPV) vaccines have been the subject of distrust with regard to their implication to trigger CD.
METHODS
From a systematic national registry, patients with first signs of CD (cases) were identified and documented for their exposure to vaccination up to 24 months before the first signs occurred. This exposure was compared to that of a representative sample of general practice patients without a history of CD, randomly selected from a national registry (referents). CD cases were 2:1 matched on age, sex, index date (ID), and region of residence. Vaccines against influenza, HPV, hepatitis B and diphtheria-tetanus-pertussis-poliomyelitis-haemophilus (DTPPHae) were considered. Associations between vaccination and CD were assessed using multivariate conditional logistic regressions, controlled for confounding factors.
FINDINGS
564 CD cases were matched to 1,128 randomly selected referents (age range: 2-79 years old). Overall, 123 (22%) CD cases and 320 (28%) referents had received at least one vaccine within 24 months before ID. Adjusted odds ratios (ORs) for any vaccination were 0.69, 95% confidence interval (CI) [0.54-0.88] with respect to any CD first signs, 0.68 [0.51-0.90] for myelitis and 0.70 [0.42-1.17] for optic neuritis. Adjusted ORs for any CD first signs were 1.02 [0.71-1.47] for influenza vaccine (administered in 9.6% of cases and 10.4% of referents) and 0.72 [0.53-0.99] for DTPPHae vaccine (administered in 10.8% of cases and 14.5% of referents). Vaccines against hepatitis B and HPV were only administered in 1.1% and 1.2% of cases and in 2.9% and 3.2% of referents respectively, which statistically explained the point estimates < 1 (ORs of 0.39 [0.16-0.94] and of 0.32 [0.13-0.80]).
INTERPRETATION
No increased risk of CD incidence was observed amongst vaccinated patients. Lower rates of vaccination against hepatitis B and HPV observed in patients with CD compared to referents may be due to the reluctance of physicians to vaccinate patients considered at risk of CD.
Topics: Humans; Child, Preschool; Child; Adolescent; Young Adult; Adult; Middle Aged; Aged; Papillomavirus Infections; Vaccination; Vaccines; Case-Control Studies; Demyelinating Diseases; Hepatitis B Vaccines
PubMed: 37351662
DOI: 10.1007/s00415-023-11822-y