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The Lancet. Microbe Jun 2024Since the emergence of the global mpox outbreak in May, 2022, more than 90 000 cases have been diagnosed across 110 countries, disproportionately affecting people with...
BACKGROUND
Since the emergence of the global mpox outbreak in May, 2022, more than 90 000 cases have been diagnosed across 110 countries, disproportionately affecting people with HIV. The durability of mpox-specific immunity is unclear and reinfections have been reported. We aimed to compare mpox immune responses up to 6 months after diagnosis in participants with and without HIV and assess their effect on disease severity and viral clearance dynamics.
METHODS
This study was embedded within a prospective, observational, multicentre cohort study of viral clearance dynamics among people with mpox in Spain (MoViE). We included women and men aged 18 years or older, who had signs of mpox, and reported having symptom onset within the previous 10 days at the moment of mpox diagnosis from three sex clinics of the Barcelona metropolitan area. Samples from skin ulcers were collected weekly to estimate the time to clear monkeypox virus (MPXV) from skin lesions. Blood samples were taken at diagnosis, 29, 91, and 182 days later for immune analysis. This included quantifying IgG and IgA against three mpox antigens by ELISA, evaluating in-vitro neutralisation, and characterising mpox-specific T-cell responses using interferon γ detecting enzyme-linked immunospot (ELISpot) assay and multiparametric flow cytometry.
FINDINGS
Of the 77 originally enrolled participants, we included 33 participants recruited between July 19, and Oct 6, 2022. Participants without HIV (19 [58%] participants) and participants with HIV (14 [42%] participants) had similar clinical severity and time to MPXV clearance in skin lesions. Participants with HIV had a CD4 T-cell count median of 777 cells per μL (IQR 484-1533), and 11 (78%) of 14 were virally suppressed on antiretroviral therapy. Nine (27%) of 33 participants were age 49 years or older. 15 (45%) of 33 participants were originally from Spain, and all participants were men. Early humoral responses, particularly concentrations and breadth of IgG and IgA, were associated with milder disease and faster viral clearance. Orthopoxvirus-specific T cells count was also positively correlated with MPXV clearance. Antibody titres declined more rapidly in participants with HIV, but T-cell responses against MPXV were sustained up to day 182 after diagnosis, regardless of HIV status.
INTERPRETATION
Higher breadth and magnitude of B-cell and T-cell responses are important in facilitating local viral clearance, limiting mpox dissemination, and reducing disease severity in individuals with preserved immune system. Antibodies appear to contribute to early viral control and T-cell responses are sustained over time, which might contribute to milder presentations during reinfection.
FUNDING
Fundació Lluita contra les Infeccions, IrsiCaixa, and Consorcio Centro de Investigación Biomédica en Red, Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación e Universidades.
PubMed: 38857615
DOI: 10.1016/S2666-5247(24)00074-0 -
Current Protocols Jun 2024Sequence changes in viral genomes generate protein sequence diversity that enables viruses to evade the host immune system, hindering the development of effective...
Sequence changes in viral genomes generate protein sequence diversity that enables viruses to evade the host immune system, hindering the development of effective preventive and therapeutic interventions. The massive proliferation of sequence data provides unprecedented opportunities to study viral adaptation and evolution. An alignment-free approach removes various restrictions posed by an alignment-dependent approach for studying sequence diversity. The publicly available tool, UNIQmin, offers an alignment-free approach for studying viral sequence diversity at any given rank of taxonomy lineage and is big data ready. The tool performs an exhaustive search to determine the minimal set of sequences required to capture the peptidome diversity within a given dataset. This compression is possible through the removal of identical sequences and unique sequences that do not contribute effectively to the peptidome diversity pool. Herein, we describe a detailed four-part protocol utilizing UNIQmin to generate the minimal set for the purpose of viral diversity analyses, alignment-free at any rank of the taxonomy lineage, using the recent global public health threat Monkeypox virus (MPX) sequence data as a case study. The protocol enables a systematic bioinformatics approach to study sequence diversity across taxonomic lineages, which is crucial for our future preparedness against viral epidemics. This is particularly important when data are abundant, freely available, and alignment is not an option. © 2024 Wiley Periodicals LLC. Basic Protocol 1: Tool installation and input file preparation Basic Protocol 2: Generation of a minimal set of sequences for a given dataset Basic Protocol 3: Comparative minimal set analysis across taxonomic lineage ranks Basic Protocol 4: Factors affecting the minimal set of sequences.
Topics: Computational Biology; Viral Proteins; Genome, Viral; Software; Viruses; Peptides
PubMed: 38856995
DOI: 10.1002/cpz1.1056 -
Cureus May 2024The case report discusses a 29-year-old male with advanced HIV who experienced one of the longest, confirmed cases of monkeypox (mpox) infection. Despite treatment with...
The case report discusses a 29-year-old male with advanced HIV who experienced one of the longest, confirmed cases of monkeypox (mpox) infection. Despite treatment with antivirals and supportive care, including intravenous tecovirimat and vaccinia immune globulin, the patient's condition worsened over a six-and-a-half-month period. He suffered from widespread ulcerative, necrotic lesions and multiple complications, including acute kidney injury, multi-drug resistant bacterial infections, and respiratory failure. Despite repeated treatments, including brincidofovir, the patient remained PCR-positive for monkeypox virus (MPXV) with low cycle threshold (Ct) values, indicating active infection. The case underscores the severity of mpox in immunocompromised individuals, particularly those with advanced HIV, and highlights the challenges in managing such cases. The patient's persistently low CD4 count and unsuppressed HIV viral load likely contributed to the inability to clear the virus. The report emphasizes the need for further research to optimize treatment strategies for MPXV infection, especially in people living with HIV.
PubMed: 38854169
DOI: 10.7759/cureus.59947 -
PLOS Global Public Health 2024
PubMed: 38848376
DOI: 10.1371/journal.pgph.0003171 -
F1000Research 2023A zoonotic, double-stranded DNA virus belonging to the genus Orthopoxvirus, the mpox virus (MPXV) is most common in tropical regions of Central and West Africa. The... (Meta-Analysis)
Meta-Analysis
BACKGROUND
A zoonotic, double-stranded DNA virus belonging to the genus Orthopoxvirus, the mpox virus (MPXV) is most common in tropical regions of Central and West Africa. The frequency of monkeypox (mpox) cases, however, has sharply climbed globally since May 2022.
OBJECTIVES
To establish the threat of mpox in terms of the oral lesions caused in sufferers.
MATERIALS AND METHODS
After a thorough study of the literature identified in the PubMed, Web of Science, and Cochrane library databases using the PRISMA framework, 103 papers were found. Using inclusion and exclusion criteria, we chose research that was relevant for our review before shortlisting 14 papers that conformed to the review's guidelines.
RESULTS
In the 14 selected studies, it was found that oral lesions were among the first clinical signs of a mpox affliction, with ulcers on the dorsal surface of tongue lips being the most common areas affected.
CONCLUSION
The rarely observed oral lesions of mpox infection may help in the diagnosis and management of this condition. It is critical to keep in mind that recognising and detecting oral lesions in mpox patients opens the door to more research and efficient patient management.
Topics: Mpox (monkeypox); Humans; Monkeypox virus; Animals; Mouth Diseases
PubMed: 38845619
DOI: 10.12688/f1000research.137363.2 -
MMWR. Morbidity and Mortality Weekly... Jun 2024In 2022, a global mpox outbreak occurred, primarily affecting gay and bisexual men who have sex with men (GBMSM). To screen for mpox's reemergence and investigate...
In 2022, a global mpox outbreak occurred, primarily affecting gay and bisexual men who have sex with men (GBMSM). To screen for mpox's reemergence and investigate potentially unsuspected cases among non-GBMSM, prospective surveillance of patients aged ≥3 months with an mpox-compatible rash (vesicular, pustular, ulcerated, or crusted) was conducted at 13 U.S. emergency departments (EDs) during June-December 2023. Demographic, historical, and illness characteristics were collected using questionnaires and electronic health records. Lesions were tested for monkeypox virus using polymerase chain reaction. Among 196 enrolled persons, the median age was 37.5 years (IQR = 21.0-53.5 years); 39 (19.9%) were aged <16 years, and 108 (55.1%) were male. Among all enrollees, 13 (6.6%) were GBMSM. Overall, approximately one half (46.4%) and one quarter (23.5%) of enrolled persons were non-Hispanic White and non-Hispanic Black or African American, respectively, and 38.8% reported Hispanic or Latino (Hispanic) ethnicity. Unstable housing was reported by 21 (10.7%) enrollees, and 24 (12.2%) lacked health insurance. The prevalence of mpox among ED patients evaluated for an mpox-compatible rash was 1.5% (95% CI = 0.3%-4.4%); all persons with a confirmed mpox diagnosis identified as GBMSM and reported being HIV-negative, not being vaccinated against mpox, and having engaged in sex with one or more partners met through smartphone dating applications. No cases were identified among women, children, or unhoused persons. Clinicians should remain vigilant for mpox and educate persons at risk for mpox about modifying behaviors that increase risk and the importance of receiving 2 appropriately spaced doses of JYNNEOS vaccine to prevent mpox.
Topics: Humans; Male; United States; Adult; Female; Young Adult; Middle Aged; Emergency Service, Hospital; Adolescent; Exanthema; Mpox (monkeypox); Disease Outbreaks; Population Surveillance; Prospective Studies
PubMed: 38843078
DOI: 10.15585/mmwr.mm7322a1 -
Analytical Chemistry Jun 2024The global spread of monkeypox has become a worldwide public healthcare issue. Therefore, there is an urgent need for accurate and sensitive detection methods to...
The global spread of monkeypox has become a worldwide public healthcare issue. Therefore, there is an urgent need for accurate and sensitive detection methods to effectively control its spreading. Herein, we screened by phage display two peptides M4 (sequence: DPCGERICSIAL) and M6 (sequence: SCSSFLCSLKVG) with good affinity and specificity to monkeypox virus (MPXV) B21R protein. To simulate the state of the peptide in the phage and to avoid spatial obstacles of the peptide, GGGSK was added at the C terminus of M4 and named as M4a. Molecular docking shows that peptide M4a and peptide M6 are bound to different epitopes of B21R by hydrogen bonds and salt-bridge interactions, respectively. Then, peptide M4a was selected as the capture probe, phage M6 as the detection probe, and carbonized polymer dots (CPDs) as the fluorescent probe, and a colorimetric and fluorescent double-signal capture peptide/antigen/signal peptide-displayed phage sandwich ELISA triggered by horseradish peroxidase (HRP) through a simple internal filtration effect (IFE) was constructed. HRP catalyzes HO to oxidize 3,3',5,5'-tetramethylbenzidine (TMB) to generate blue oxidized TMB, which can further quench the fluorescence of CPDs through IFE, enabling to detect MPXV B21R in colorimetric and fluorescent modes. The proposed simple immunoassay platform shows good sensitivity and reliability in MPXV B21R detection. The limit of detection for colorimetric and fluorescent modes was 27.8 and 9.14 pg/mL MPXV B21R, respectively. Thus, the established double-peptide sandwich-based dual-signal immunoassay provides guidance for the development of reliable and sensitive antigen detection capable of mutual confirmation, which also has great potential for exploring various analytical strategies for other respiratory virus surveillance.
Topics: Enzyme-Linked Immunosorbent Assay; Peptides; Antigens, Viral; Molecular Docking Simulation; Horseradish Peroxidase; Limit of Detection; Fluorescent Dyes; Peptide Library; Benzidines; Colorimetry
PubMed: 38842443
DOI: 10.1021/acs.analchem.4c01802 -
Exploring the dynamics of monkeypox transmission with data-driven methods and a deterministic model.Frontiers in Epidemiology 2024Mpox (formerly monkeypox) is an infectious disease that spreads mostly through direct contact with infected animals or people's blood, bodily fluids, or cutaneous or...
INTRODUCTION
Mpox (formerly monkeypox) is an infectious disease that spreads mostly through direct contact with infected animals or people's blood, bodily fluids, or cutaneous or mucosal lesions. In light of the global outbreak that occurred in 2022-2023, in this paper, we analyzed global Mpox univariate time series data and provided a comprehensive analysis of disease outbreaks across the world, including the USA with Brazil and three continents: North America, South America, and Europe. The novelty of this study is that it delved into the Mpox time series data by implementing the data-driven methods and a mathematical model concurrently-an aspect not typically addressed in the existing literature. The study is also important because implementing these models concurrently improved our predictions' reliability for infectious diseases.
METHODS
We proposed a traditional compartmental model and also implemented deep learning models (1D- convolutional neural network (CNN), long-short term memory (LSTM), bidirectional LSTM (BiLSTM), hybrid CNN-LSTM, and CNN-BiLSTM) as well as statistical time series models: autoregressive integrated moving average (ARIMA) and exponential smoothing on the Mpox data. We also employed the least squares method fitting to estimate the essential epidemiological parameters in the proposed deterministic model.
RESULTS
The primary finding of the deterministic model is that vaccination rates can flatten the curve of infected dynamics and influence the basic reproduction number. Through the numerical simulations, we determined that increased vaccination among the susceptible human population is crucial to control disease transmission. Moreover, in case of an outbreak, our model showed the potential for epidemic control by adjusting the key epidemiological parameters, namely the baseline contact rate and the proportion of contacts within the human population. Next, we analyzed data-driven models that contribute to a comprehensive understanding of disease dynamics in different locations. Additionally, we trained models to provide short-term (eight-week) predictions across various geographical locations, and all eight models produced reliable results.
CONCLUSION
This study utilized a comprehensive framework to investigate univariate time series data to understand the dynamics of Mpox transmission. The prediction showed that Mpox is in its die-out situation as of July 29, 2023. Moreover, the deterministic model showed the importance of the Mpox vaccination in mitigating the Mpox transmission and highlighted the significance of effectively adjusting key epidemiological parameters during outbreaks, particularly the contact rate in high-risk groups.
PubMed: 38840980
DOI: 10.3389/fepid.2024.1334964 -
Ear, Nose, & Throat Journal Jun 2024
PubMed: 38840528
DOI: 10.1177/01455613241260769 -
Virology Journal Jun 2024Limited data is available regarding the severity and mortality of Mpox in individuals with immunocompromised conditions. Therefore, we performed this meta-analysis to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Limited data is available regarding the severity and mortality of Mpox in individuals with immunocompromised conditions. Therefore, we performed this meta-analysis to understand the impact of HIV- or non-HIV-associated immunosuppression on the severity of Mpox requiring hospitalization and mortality.
METHODS
A thorough literature search was performed from 2022 up to January 2024. The results were presented as odds ratios (ORs). We only included patients who required hospitalization for severity rather than isolation.
RESULTS
A total of 34 studies were included in this analysis. Our analysis did not find a significant difference in the hospitalization risk between HIV-positive individuals and those who were HIV-negative (OR = 1.03; P = 0.85; 7 studies; CD4 count of fewer than 200 cells/µL was less than 0.5% across all studies). Patients with a CD4 count lower than 200 cells/µL or an unsuppressed RNA viral load (> 200 copies/ml) had a significantly higher hospitalization risk (OR = 5.3, P < 0.001) and (OR = 3, P < 0.001), respectively. Most of the reported deaths were reported in patients with HIV with CD4 counts below 200 cells/µL, with some fatal cases occurring in non-HIV immunosuppressed patients, particularly organ transplant recipients. Based on the autopsy findings, Mpox was confirmed in multiple organs, particularly the digestive tract, lung, and testes. Furthermore, some studies documented cases of death that were suspected to be related to hemophagocytic lymphohistiocytosis (HLH) and immune reconstitution inflammatory syndrome (IRIS). Most of the death reports showed concomitant non-Mpox infections at the time of hospitalization and death CONCLUSIONS: Our finding shows that Mpox acts as an opportunistic pathogen in immunocompromised individuals. These individuals should be prioritized for early care and closely monitored for signs of deteriorating clinical conditions. Clinical manifestations and autopsy findings strongly suggest Mpox dissemination to multiple organs, particularly the digestive tract, and lungs. However, the presence of concomitant non-Mpox infections complicates the assessment of the attribution of Mpox to death. Caution should be exercised when interpreting data suggesting poorer outcomes in individuals with non-HIV immunosuppression, as current evidence is scarce and further research is needed.
Topics: Humans; Hospitalization; Immunocompromised Host; HIV Infections; CD4 Lymphocyte Count; Mpox (monkeypox); Disease Outbreaks; Immunosuppression Therapy; Viral Load
PubMed: 38840177
DOI: 10.1186/s12985-024-02392-0