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Indian Journal of Pharmacology Mar 2024The virus known as monkeypox is the source of the zoonotic disease monkeypox, which was historically widespread in Central Africa and West Africa. The cases of monkeypox... (Review)
Review
The virus known as monkeypox is the source of the zoonotic disease monkeypox, which was historically widespread in Central Africa and West Africa. The cases of monkeypox in humans are uncommon outside of West and Central Africa, but copious nonendemic nations outside of Africa have recently confirmed cases. People when interact with diseased animals, then, they may inadvertently contact monkeypox. There are two drugs in the market: brincidofovir and tecovirimat and both of these drugs are permitted for the cure of monkeypox by the US Food and Drug Administration. The present review summarizes the various parameters of monkeypox in context with transmission, signs and symptoms, histopathological and etiological changes, and possible treatment. Monkeypox is clinically similar to that of smallpox infection but epidemiologically, these two are different, the present study also signifies the main differences and similarities of monkeypox to that of other infectious diseases. As it is an emerging disease, it is important to know about the various factors related to monkeypox so as to control it on a very early stage of transmission.
Topics: Mpox (monkeypox); Humans; Animals; Antiviral Agents; Communicable Diseases, Emerging; Cytosine; Monkeypox virus; Isoindoles; Organothiophosphorus Compounds; Organophosphonates; Benzamides; Phthalimides
PubMed: 38687317
DOI: 10.4103/ijp.ijp_156_23 -
Viruses Apr 2024To evaluate whether antibodies specific for the vaccinia virus (VV) are still detectable after at least 45 years from immunization. To confirm that VV-specific...
AIMS
To evaluate whether antibodies specific for the vaccinia virus (VV) are still detectable after at least 45 years from immunization. To confirm that VV-specific antibodies are endowed with the capacity to neutralize Mpox virus (MPXV) in vitro. To test a possible role of polyclonal non-specific activation in the maintenance of immunologic memory.
METHODS
Sera were collected from the following groups: smallpox-vaccinated individuals with or without latent tuberculosis infection (LTBI), unvaccinated donors, and convalescent individuals after MPXV infection. Supernatant of VV- or MPXV-infected Vero cells were inactivated and used as antigens in ELISA or in Western blot (WB) analyses. An MPXV plaque reduction neutralization test (PRNT) was optimized and performed on study samples. VV- and PPD-specific memory T cells were measured by flow cytometry.
RESULTS
None of the smallpox unvaccinated donors tested positive in ELISA or WB analysis and their sera were unable to neutralize MPXV in vitro. Sera from all the individuals convalescing from an MPXV infection tested positive for anti-VV or MPXV IgG with high titers and showed MPXV in vitro neutralization capacity. Sera from most of the vaccinated individuals showed IgG anti-VV and anti-MPXV at high titers. WB analyses showed that positive sera from vaccinated or convalescent individuals recognized both VV and MPXV antigens. Higher VV-specific IgG titer and specific T cells were observed in LTBI individuals.
CONCLUSIONS
ELISA and WB performed using supernatant of VV- or MPXV-infected cells are suitable to identify individuals vaccinated against smallpox at more than 45 years from immunization and individuals convalescing from a recent MPXV infection. ELISA and WB results show a good correlation with PRNT. Data confirm that a smallpox vaccination induces a long-lasting memory in terms of specific IgG and that antibodies raised against VV may neutralize MPXV in vitro. Finally, higher titers of VV-specific antibodies and higher frequency of VV-specific memory T cells in LTBI individuals suggest a role of polyclonal non-specific activation in the maintenance of immunologic memory.
Topics: Humans; Antibodies, Viral; Smallpox Vaccine; B-Lymphocytes; Antibodies, Neutralizing; Cross Reactions; Vaccinia virus; Middle Aged; Immunologic Memory; Neutralization Tests; Smallpox; Animals; Male; T-Lymphocytes; Female; Enzyme-Linked Immunosorbent Assay; Orthopoxvirus; Vaccination; Chlorocebus aethiops; Adult; Lymphocyte Activation; Vero Cells
PubMed: 38675961
DOI: 10.3390/v16040620 -
Vaccines Apr 2024The global outbreak of the 2022 monkeypox virus infection of humans and the 2023 documentation of a more virulent monkeypox in the Democratic Republic of the Congo...
The global outbreak of the 2022 monkeypox virus infection of humans and the 2023 documentation of a more virulent monkeypox in the Democratic Republic of the Congo raised public health concerns about the threat of human-to-human transmission of zoonotic diseases. Currently available vaccines may not be sufficient to contain outbreaks of a more transmissible and pathogenic orthopoxvirus. Development of a safe, effective, and scalable vaccine against orthopoxviruses to stockpile for future emergencies is imminent. In this study, we have developed an mRNA vaccine candidate, ALAB-LNP, expressing four vaccinia viral antigens A27, L1, A33, and B5 in tandem in one molecule, and evaluated the vaccine immunogenicity in rodent models. Immunization of animals with the candidate mRNA vaccine induced a potent cellular immune response and long-lasting antigen-specific binding antibody and neutralizing antibody responses against vaccinia virus. Strikingly, the sera from the vaccine-immunized mice cross-reacted with all four homologous antigens of multiple orthopoxviruses and neutralized monkeypox virus in vitro, holding promise for this mRNA vaccine candidate to be used for protection of humans from the infection of monkeypox and other orthopoxvirus.
PubMed: 38675767
DOI: 10.3390/vaccines12040385 -
Microorganisms Mar 2024In 2022-23, the human monkeypox virus (MPXV) caused a global outbreak in several non-endemic countries. Here, we evaluated the diagnostic performance of four...
In 2022-23, the human monkeypox virus (MPXV) caused a global outbreak in several non-endemic countries. Here, we evaluated the diagnostic performance of four qualitative PCR assays for the laboratory diagnosis of mpox (monkeypox) monkeypox disease. From July to August 2022, 27 positive and 10 negative specimens (lesion, crust and exudate swabs) were tested in the laboratory of the Hygiene Unit of the San Martino Hospital (Genoa, Italy) by using home-made real-time PCR to detect MPXV generic G2R_G DNA. According to the manufacturer's instructions, we also retrospectively analyzed these specimens using RealCycler MONK-UX/-GX (Progenie Molecular), STANDARD M10 MPX/OPX (SD Biosensor), Novaplex MPXV (Seegene Inc.) and RealStar Orthopoxvirus PCR Kit 1.0 (Altona Diagnostics) assays, recognized as research-use-only tests. The diagnostic accuracy and sensitivity of these assays ranged from 97.3% (95% CI: 86.2-99.5%) to 100% (95% CI: 90.6-100%) and 96.3% (95% CI: 81.72-99.34%) to 100% (95% CI: 72.2-100%), respectively. The RealCycler MONK-UX and STANDARD M10 MPX/OPX did not detect one positive sample with a cycle threshold of 36. The overall specificity was 100% (95% CI: 72.2-100%), and Cohen's Kappa values ranged from 1 (95% CI: 0.67-1) to 0.93 (95% CI: 0.61-1). As they are highly accurate, reliable and user-friendly, these tests should be recommended for the routine or rapid laboratory discrimination of mpox from other rash illnesses.
PubMed: 38674608
DOI: 10.3390/microorganisms12040664 -
International Journal of Molecular... Apr 2024Virotherapy is one of the perspective technologies in the treatment of malignant neoplasms. Previously, we have developed oncolytic vaccinia virus VV-GMCSF-Lact and its...
Virotherapy is one of the perspective technologies in the treatment of malignant neoplasms. Previously, we have developed oncolytic vaccinia virus VV-GMCSF-Lact and its high cytotoxic activity and antitumor efficacy against glioma was shown. In this work, using immortalized and patient-derived cells with different sensitivity to VV-GMCSF-Lact, we evaluated the cytotoxic effect of chemotherapy agents. Additionally, we studied the combination of VV-GMCSF-Lact with temozolomide which is the most preferred drug for glioma treatment. Experimental results indicate that first adding temozolomide and then the virus to the cells is inherently more efficient than dosing it in the reverse order. Testing these regimens in the U87 MG xenograft glioblastoma model confirmed this effect, as assessed by tumor growth inhibition index and histological analysis. Moreover, VV-GMCSF-Lact as monotherapy is more effective against U87 MG glioblastoma xenografts comparing temozolomide.
Topics: Humans; Animals; Oncolytic Virotherapy; Oncolytic Viruses; Temozolomide; Xenograft Model Antitumor Assays; Cell Line, Tumor; Mice; Glioma; Vaccinia virus; Granulocyte-Macrophage Colony-Stimulating Factor; Brain Neoplasms; Mice, Nude; Antineoplastic Agents; Glioblastoma; Combined Modality Therapy
PubMed: 38673835
DOI: 10.3390/ijms25084244 -
Journal of Clinical Medicine Apr 2024Mpox, caused by viruses of the genus Orthopoxvirus, is an emerging threat to human and animal health. With increasing urbanization and more frequent interaction between... (Review)
Review
Mpox, caused by viruses of the genus Orthopoxvirus, is an emerging threat to human and animal health. With increasing urbanization and more frequent interaction between humans and wild animals, the risk of Mpox transmission to humans has increased significantly. This review aims to examine in depth the epidemiology, pathogenesis, and diagnosis of Mpox, with a special focus on recent discoveries and advances in understanding the disease. Molecular mechanisms involved in viral replication will be examined, as well as risk factors associated with interspecific transmission and spread of the disease in human populations. Currently available diagnostic methods will also be discussed, with a critical analysis of their limitations and possible future directions for improving the accuracy and timeliness of diagnosis. Finally, this review will explore the public health implications associated with Mpox, emphasizing the importance of epidemiological surveillance, vaccination, and emergency preparedness to prevent and manage possible outbreaks. Understanding the epidemiology and control strategies for Mpox is critical to protecting the health of human and animal communities and mitigating the risk of interspecific transmission and spread of the disease.
PubMed: 38673507
DOI: 10.3390/jcm13082234 -
Euro Surveillance : Bulletin Europeen... Apr 2024BackgroundFollowing the 2022-2023 mpox outbreak, crucial knowledge gaps exist regarding orthopoxvirus-specific immunity in risk groups and its impact on future...
BackgroundFollowing the 2022-2023 mpox outbreak, crucial knowledge gaps exist regarding orthopoxvirus-specific immunity in risk groups and its impact on future outbreaks.AimWe combined cross-sectional seroprevalence studies in two cities in the Netherlands with mathematical modelling to evaluate scenarios of future mpox outbreaks among men who have sex with men (MSM).MethodsSerum samples were obtained from 1,065 MSM attending Centres for Sexual Health (CSH) in Rotterdam or Amsterdam following the peak of the Dutch mpox outbreak and the introduction of vaccination. For MSM visiting the Rotterdam CSH, sera were linked to epidemiological and vaccination data. An in-house developed ELISA was used to detect vaccinia virus (VACV)-specific IgG. These observations were combined with published data on serial interval and vaccine effectiveness to inform a stochastic transmission model that estimates the risk of future mpox outbreaks.ResultsThe seroprevalence of VACV-specific antibodies was 45.4% and 47.1% in Rotterdam and Amsterdam, respectively. Transmission modelling showed that the impact of risk group vaccination on the original outbreak was likely small. However, assuming different scenarios, the number of mpox cases in a future outbreak would be markedly reduced because of vaccination. Simultaneously, the current level of immunity alone may not prevent future outbreaks. Maintaining a short time-to-diagnosis is a key component of any strategy to prevent new outbreaks.ConclusionOur findings indicate a reduced likelihood of large future mpox outbreaks among MSM in the Netherlands under current conditions, but emphasise the importance of maintaining population immunity, diagnostic capacities and disease awareness.
Topics: Humans; Male; Netherlands; Seroepidemiologic Studies; Cross-Sectional Studies; Disease Outbreaks; Homosexuality, Male; Adult; Middle Aged; Vaccinia; Antibodies, Viral; Vaccination; Young Adult; Models, Theoretical; Enzyme-Linked Immunosorbent Assay; Immunoglobulin G
PubMed: 38666400
DOI: 10.2807/1560-7917.ES.2024.29.17.2300532 -
International Journal of Paleopathology Jun 2024This project seeks to create a differential diagnosis for lesions found on the skeletal remains of two children as a means to explore the presence of viral disease in...
OBJECTIVE
This project seeks to create a differential diagnosis for lesions found on the skeletal remains of two children as a means to explore the presence of viral disease in 16th- century Peru.
MATERIALS
Extremely well-preserved human remains of two children who died between the ages of 1-2 years old, recovered from the circum-contact (∼1540 CE) cemetery in Huanchaco, Peru.
METHODS
Macroscopic and radiographic analysis.
RESULTS
Both individuals present with cortical thickening, symmetrical destructive lesions, metaphyseal expansion, perforations, exposure of the medullary cavity, resorption of metaphyseal ends and necrosis of the long bones, and deposited reactive new bone. These features are consistent with osteomyelitis variolosa and bacterial osteomyelitis.
CONCLUSIONS
Three features of Individuals IG-124 and IG-493 suggest a highly consistent diagnosis of osteomyelitis variolosa: multiple skeletal lesions, the historical context of the area, and the high mortality rate of non-adults in the circum-contact cemetery.
SIGNIFICANCE
Although viral infections are ubiquitous and well documented historically, their etiologies are often difficult to determine in archaeological populations. Orthopoxvirus variola (smallpox) is one of the many viruses whose archaeological impact is still under explored in skeletal remains.
LIMITATIONS
The absence of smallpox in other children from the Huanchaco cemetery creates difficulty in ascertaining true prevalence rates or information on potential outbreaks.
SUGGESTIONS FOR FURTHER RESEARCH
Further research analyzing aDNA from calculus and/or residues using a DIP-GC-MS method might create a better understanding of how smallpox spread through the region.
Topics: Humans; Smallpox; Peru; History, 16th Century; Infant; Child, Preschool; Male; Osteomyelitis; Paleopathology; Female; Cemeteries
PubMed: 38653101
DOI: 10.1016/j.ijpp.2024.04.002 -
Open Forum Infectious Diseases Apr 2024Though typically self-limiting, severe mpox infections have been treated with antiviral medications, most notably tecovirimat. Various reports exist of mpox progression...
Though typically self-limiting, severe mpox infections have been treated with antiviral medications, most notably tecovirimat. Various reports exist of mpox progression despite tecovirimat treatment. Treatment resistance can be due to acquired mpox strain mutations, most often occurring in an immunocompromised host. We present the case of a male with AIDS who developed disseminated treatment-resistant mpox infection complicated by superimposed bacterial and fungal infections. His orthopoxvirus polymerase chain reaction result remained positive despite treatment with 4 weeks of oral tecovirimat and 3 doses of intravenous cidofovir. Poor response to antiviral therapy was likely due to his underlying immunocompromised state; however, strain resistance cannot be ruled out given that the patient had started but not completed a 14-day course of tecovirimat 8 months prior, at the time of initial mpox diagnosis. Patients with mpox who are immunocompromised may require extended and additional treatment beyond the standard 14 days of tecovirimat, such as cidofovir, brincidofovir, or intravenous vaccina immune globulin.
PubMed: 38651138
DOI: 10.1093/ofid/ofae138 -
One Health (Amsterdam, Netherlands) Jun 2024The human population in Guyana, located on the South American continent, is vulnerable to zoonotic diseases due to an appreciable reliance on Neotropical wildlife as a...
BACKGROUND
The human population in Guyana, located on the South American continent, is vulnerable to zoonotic diseases due to an appreciable reliance on Neotropical wildlife as a food source and for trade. An existing suboptimal health surveillance system may affect the effective monitoring of important zoonotic diseases. To effectively address this deficit, a One Health zoonotic disease prioritization workshop was conducted to identify nationally significant zoonoses.
METHODS
Prioritization of zoonotic diseases was conducted for the first time in Guyana & Caribbean region using literature review, prioritization criteria and a risk prioritization tool in combination with a consultative One Health workshop. This involved multisectoral experts from varied disciplines of social, human, animal, and environmental health to prioritize zoonotic diseases using a modified semi-quantitative One Health Zoonotic Disease Prioritization (OHZDP) tool. The inclusion and exclusion criteria were applied to pathogen hazards in existence among wildlife in Guyana during the hazard identification phase.
RESULTS
In total, fifty zoonoses were chosen for prioritization. Based on their weighted score, prioritized diseases were ranked in order of relative importance using a one-to-five selection scale. In Guyana, this zoonotic disease prioritization method is the first significant step toward bringing together specialists from the fields of human, animal, and environmental health. Following discussion of the OHZDP Tool output among disease experts, a final zoonotic disease list, including tuberculosis, leptospirosis, gastroenteritis, rabies, coronavirus, orthopoxvirus, viral hemorrhagic fevers, and hepatitis were identified as the top eight priority zoonoses in Guyana.
CONCLUSIONS
This represents the first prioritization of nationally significant zoonotic diseases in Guyana and the English-speaking Caribbean. This One Health strategy to prioritize these eight zoonoses of wildlife origin is a step that will support future tracking and monitoring for disease prevalence among humans and wildlife and can be used as a decision-making guide for policymakers and stakeholders in Guyana.
PubMed: 38644970
DOI: 10.1016/j.onehlt.2024.100730