Multi-country Outbreak Research Articles

Current and Perspective Sensing Methods for Monkeypox Virus.

The outbreak of the monkeypox virus (MPXV) in non-endemic countries is an emerging global health threat and may have an economic impact if proactive actions are not taken. As shown by the COVID-19 pandemic, rapid, accurate, and cost-effective virus detection techniques play a pivotal role in disease diagnosis and control. Considering the sudden multicountry MPXV outbreak, a critical evaluation of the MPXV detection approaches would be a timely addition to the endeavors in progress for MPXV control and prevention. Herein, we evaluate the current MPXV detection methods, discuss their pros and cons, and provide recommended solutions to the problems. We review the traditional and emerging nucleic acid detection approaches, immunodiagnostics, whole-particle detection, and imaging-based MPXV detection techniques. The insights provided in this article will help researchers to develop novel techniques for the diagnosis of MPXV.

Letter to editor: human monkeypox and the atypical outbreak

Dear editor, we would like to share ideas on the publication in your journal "Learning from the past: the history of human monkeypox and the atypical multi-country outbreak in 2022"[ 1]. To better understand the risk assessment and potential clinical and public health impacts of this outbreak in the future, Yao[ 1] provides a thought-provoking history of the 64-year interaction between the monkeypox virus and humans. He also provides a variety of information and viewpoints on the human monkeypox outbreak.

Monkeypox: An Emerging Global Public Health Emergency.

The virus causing monkeypox, a rare zoonotic viral disease, belongs to the Poxviridae family and the Orthopoxvirus genus. On 23 July 2022, the World Health Organization (WHO) declared the monkeypox outbreak as a Public Health Emergency of International Concern (PHEIC). From May to July 2022, a multi-country outbreak of monkeypox was reported in both endemic and non-endemic regions. Major goals of managing monkeypox are to identify the suspected cases, detect generic orthopoxvirus DNA at a state or commercial laboratory, and establish the Centers for Disease Control and Prevention real-time polymerase chain reaction testing. Currently, there are no approved treatments for monkeypox virus infection. However, a variety of antiviral medications originally designed for the treatment of smallpox and other viral infections could be considered. Pre-exposure prophylaxis for laboratory and health care employees and post-exposure prophylaxis for individuals with high-risk or intermediate-risk exposures are to be considered. The CDC Emergency Operations Center is available for advice on the appropriate use of medical countermeasures, and can help in obtaining antiviral drugs and vaccines from the National Strategic Stockpile. This review gives an overview of the global scenario, clinical presentation, and management of monkeypox in the light of a global public health emergency.

Study of the first clinical cases on monkeypox in Poland.

Monkeypox is a viral, zoonotic, emerging infectious disease that has become the most significant orthopoxviral infection among humans since the eradication of smallpox. It is endemic in Central and West Africa, and since May 2022 it has caused a multi-country outbreak in six continents. So far, no clinical cases of this disease have been observed in Poland. Monkeypox can be transmitted by any person, regardless of gender identity or sexual preferences, through direct contact with the secretion from skin lesions or through fomites contaminated with infectious material. Therefore, people infected with the monkeypox virus require isolation until the skin lesions heal completely and the scabs fall off, which is equivalent to the end of their infectivity. The paper presents a study of the first nine clinical cases of monkeypox in Poland, along with photographic documentation. All patients were young men, the vast majority of whom had contact with multiple sexual partners, and presented a higher prevalence of human immunodeficiency virus (HIV) infection than in the general population. The course of the disease was self-limited and no specific antiviral treatment was required by any of the patients. Nonetheless, there was a change in the route of transmission of the infection to sexual contact and an atypical clinical course of the disease, which resulted both in skin lesions initially appearing in the anogenital area, skin lesions occurring at various stages of development, and the appearance of skin lesions before the onset of general symptoms. In one of the patients, skin changes were not observed at all.

A Curious Case of Severe Proctitis

Question: A 40-year-old man with well controlled human immunodeficiency virus presented to the emergency department with one week of severe rectal pain. He subsequently developed fevers and hematochezia with loose stools, prompting him to seek care. Past sexual history includes anal receptive intercourse and a previous diagnosis of anal human papilloma virus. On presentation, he was febrile to 103.2°F, but otherwise hemodynamically stable. Rectal exam was limited by severe pain, but was notable for mucopurulent discharge, perianal ulcers, and erythema (Figure A). Laboratory testing was significant for leukocytosis with white blood cell count of 12.6 /mm3 and an elevated C-reactive protein of 111 mg/L. A computed tomographic scan of his abdomen with intravenous contrast was performed and showed marked inflammatory changes of the rectum and surrounding soft tissue without abscess or other upstream colonic inflammation and multiple enlarged perirectal and retroperitoneal lymph nodes (Figure B). Extensive testing for multiple infectious diseases, including syphilis, herpes simplex virus, gonorrhea, and chlamydia, was negative. What is the diagnosis? Look on page 528 for the answer and see the Gastroenterology website (www.gastrojournal.org) for more information on submitting to Gastro Curbside Consult. Given high index of suspicion, he was placed on our standard precautions for monkeypox rule-out, which includes isolated room, gowns, gloves, eye protection, and N-95 filter. A rectal polymerase chain reaction swab for nonvariola orthopox virus returned positive, confirming a diagnosis of monkeypox virus. This was reported to the State Department of Health for contact tracing. The patient was treated with tecovirimat antiviral therapy under emergency use authorization, as approved by the Center for Disease Control and State Department of Health. He noted symptomatic improvement within a few days and was discharged to complete an oral course of 600 mg tecovirimat twice daily for a total of 14 days. Monkeypox virus is a zoonotic orthopox DNA virus that was previously endemic to Africa.1Thornhill J.P. Barkati S. Walmsley S. et al.Monkeypox virus infection in humans across 16 countries—April-June 2022.N Engl J Med. 2022; 387: 679-691Crossref PubMed Scopus (508) Google Scholar In the spring of 2022, cases outside of endemic regions began to rise and a global outbreak began. The presenting symptoms of monkeypox can be nonspecific, including fevers, myalgias, mucosal involvement, and skin lesions, which are vesicular and evolve over days to weeks.1Thornhill J.P. Barkati S. Walmsley S. et al.Monkeypox virus infection in humans across 16 countries—April-June 2022.N Engl J Med. 2022; 387: 679-691Crossref PubMed Scopus (508) Google Scholar Monkeypox has now been declared a public health emergency, and this case highlights many important considerations for diagnosis and treatment. First, the current monkeypox outbreak is disproportionately affecting men who have sex with men.2Guarner J. del Rio C. Malani P.N. Monkeypox in 2022—what clinicians need to know.JAMA. 2022; 328: 139-140Crossref PubMed Scopus (70) Google Scholar Transmission is thought to occur through to skin-to-skin contact. The lesions typically appear first at the site of inoculation, and thus anal/genital lesions may be more common. In a recent international case series published in the New England Journal of Medicine, 73% of the 528 patients with polymerase chain reaction–diagnosed monkeypox had anogenital ulcerations.1Thornhill J.P. Barkati S. Walmsley S. et al.Monkeypox virus infection in humans across 16 countries—April-June 2022.N Engl J Med. 2022; 387: 679-691Crossref PubMed Scopus (508) Google Scholar Also noted in that case series, the most common cause of hospitalization was anorectal pain.1Thornhill J.P. Barkati S. Walmsley S. et al.Monkeypox virus infection in humans across 16 countries—April-June 2022.N Engl J Med. 2022; 387: 679-691Crossref PubMed Scopus (508) Google Scholar The was true for our patient, who required intravenous pain medication on presentation. Symptomatic treatment with opioids, ibuprofen, topical anesthetics (lidocaine jelly per rectum), and stool softeners provided mild improvement while the patient was admitted. However, starting tecovirimat provided the greatest symptomatic improvement, and the patient was able to be discharged with only ibuprofen and stool softeners for pain control after 2 days of treatment. The World Health Organization believes the true number of monkeypox to be underestimated owing to lack of recognition of this infection that was previously only seen in a few countries.3World Health Organization Multi-country monkeypox outbreak: situation update. June 27, 2022.https://www.who.int/emergencies/disease-outbreak-news/item/2022-DON396Google Scholar Thus, a high degree of suspicion must be maintained for the disease, even in patients with isolated anal ulceration or proctitis

Monkeypox: A Comprehensive Review.

The 2022 multi-country monkeypox outbreak in humans has brought new public health adversity on top of the ongoing coronavirus disease 2019 (COVID-19) pandemic. The disease has spread to 104 countries throughout six continents of the world, with the highest burden in North America and Europe. The etiologic agent, monkeypox virus (MPXV), has been known since 1959 after isolation from infected monkeys, and virulence among humans has been reported since the 1970s, mainly in endemic countries in West and Central Africa. However, the disease has re-emerged in 2022 at an unprecedented pace, with particular concern on its human-to-human transmissibility and community spread in non-endemic regions. As a mitigation effort, healthcare workers, public health policymakers, and the general public worldwide need to be well-informed on this relatively neglected viral disease. Here, we provide a comprehensive and up-to-date overview of monkeypox, including the following aspects: epidemiology, etiology, pathogenesis, clinical features, diagnosis, and management. In addition, the current review discusses the preventive and control measures, the latest vaccine developments, and the future research areas in this re-emerging viral disease that was declared as a public health emergency of international concern.

Monkeypox outbreak in a piercing and tattoo establishment in Spain

Monkeypox outbreak in a piercing and tattoo establishment in Spain

Monkeypox Outbreak - 2022: A Brief Review

Monkeypox is a zoonotic viral disease caused by Monkeypox virus belonging to Orthopoxvirus. The virus is present in monkeys and small rodents such as squirrels, ant-eaters and others. First human case was reported from Democratic Republic of the Congo in 1970 and had been reported only from central and western African countries before 2022. This year, the first human case of monkeypox was confirmed on May 7, 2022 in UK who travelled to Nigeria. Thereafter, the disease has caused a multi-country outbreak involving all continents outside Africa. As of August 28, 2022, a total of 47,652 monkeypox cases have been reported from 99 countries that have not historically reported monkeypox and in 7 countries that have historically reported monkeypox. Of the total, 47,209 cases have occurred in countries that have not historically reported monkeypox with a highest numbers of cases (17,431) in USA. Keeping in view of an increasing number of cases “monkeypox emergency” has been declared by US government on August 4, 2022. Second highest numbers of cases have been reported from Spain (6,459), Brazil (3,984), France (3,421), Germany (3,405), Britain (3,207) and following by other countries as of August 28, 2022. No cases has been reported from Nepal as of August 28, 2022.

Fludarabine, a Potential DNA-Dependent RNA Polymerase Inhibitor, as a Prospective Drug against Monkeypox Virus: A Computational Approach.

Monkeypox is a zoonotic contagious disease that has recently re-emerged in different countries worldwide. Due to the lack of an effective treatment that eliminates the virus, there is an urgent need to find effective drugs to stop the spread of the multi-country outbreak. The current study aimed to use computational methods to quickly identify potentially effective drugs against the Monkeypox virus (MPXV). Three MPXV proteins were targeted in this study due to their essential role in viral replication (a DNA-Dependent RNA Polymerase subunit (A6R)), a protein involved in cell entry (D8L), and a protein catalyzing the envelopment of intracellular mature virus particles (F13L). We virtually screened a library of 1615 FDA-approved compounds, utilizing different in-silico approaches including computational modeling, molecular docking, molecular dynamic (MD) simulation, and MM-GBSA. The compound Fludarabine was found to have the best docking score (−7.53 kcal/mol) in relation to the MPXV A6R protein. Additionally, Fludarabine showed in-silico activity on the D8L and F13L proteins. During the whole period of the 100 ns MD simulation, the complex of A6R and Fludarabine exhibited the best stability. This stability was reflected in a good score of MM-GBSA, with an average value of −44.62 kcal/mole in a range between −53.26 and −35.49 and a low value of standard deviation (3.76). Furthermore, Fludarabine blocked efficiently the Asn175 residue which has an important role in the attachment of the virus to a host cell. The results of this study recommend more in vitro studies on this compound, as a starting point to develop a novel treatment against MPXV.

A large multi-country outbreak of monkeypox across 41 countries in the WHO European Region, 7 March to 23 August 2022.

Following the report of a non-travel-associated cluster of monkeypox cases by the United Kingdom in May 2022, 41 countries across the WHO European Region have reported 21,098 cases and two deaths by 23 August 2022. Nowcasting suggests a plateauing in case notifications. Most cases (97%) are MSM, with atypical rash-illness presentation. Spread is mainly through close contact during sexual activities. Few cases are reported among women and children. Targeted interventions of at-risk groups are needed to stop further transmission.

Viral Adaptation, Vulnerable Health Care Systems and Health Inequities: Monkeypox as an emerging threat in the Global Health Agenda

Due to the increasing number of monkeypox virus (MPXV) cases, WHO declared it a Public Health Emergency of International Concern (PHEIC). The transmission of monkeypox has been described during this outbreak associated with close sexual contact through the skin with infectious lesions. It is not very clear whether this virus is better adapting to human-human transmission, we do not know if the case fatality rate is being lower during the current global spread due to genetic changes in the virus or as an effect of a better understanding of the actual number of mild cases of infections. The emergence of pathogens, particularly the spillover of zoonotic viruses, is not a totally unpredictable phenomenon, the current monkeypox multi-country outbreak was preceded by a progressive increase in the number of cases in recent decades and changes in the epidemiological profile in affected areas of Africa. We must resume the conversation with civil society organizations, bring a more sex-positive health discourse through a healthy and stigma-free scientific dialogue.

Monkeypox virus genome sequence from an imported human case in Colombia.

Introduction: Monkeypox virus (MPXV) is an enveloped double-stranded DNA virus with a genome of approximately 197.209 bp. The current classification divides MPXV into three clades: Clade I (Central African or Congo Basin clade) and clades IIa and IIb (West African clades).Objective: To report the complete genome and phylogenetic analysis of a human monkeypox case detected in Colombia.Materials and methods: Exudate from vesicular lesions was obtained from a male patient with recent travel history to Spain. A direct genomic approach was implemented in which total DNA from the sample was purified through a column-based method, followed by sequencing on the Nanopore GridION. Reads were aligned against the MPXV reference genome using minimap2 v.2.24 and phylogenetic inference was performed using maximum likelihood estimation.Results: A total of 11.951 reads mapped directly to a reference genome with 96.8% of coverage (190.898 bp).Conclusion: Phylogenetic analysis of the MPXV circulating in Colombia demonstrated its close relationship to clade IIb responsible for the multi-country outbreak in 2022.

Epidemiologic Features and Control Measures during Monkeypox Outbreak, Spain, June 2022.

During June 2022, Spain was one of the countries most affected worldwide by a multicountry monkeypox outbreak with chains of transmission without identified links to disease-endemic countries. We provide epidemiologic features of cases reported in Spain and the coordinated measures taken to respond to this outbreak.

Monkeypox Knowledge and Confidence in Diagnosis and Management with Evaluation of Emerging Virus Infection Conspiracies among Health Professionals in Kuwait.

As the 2022 human monkeypox (HMPX) multi-country outbreak is spreading, the response of healthcare workers (HCWs) is central to mitigation efforts. The current study aimed to evaluate HMPX knowledge and confidence in diagnosis and management among HCWs in Kuwait. We used a self-administered questionnaire distributed in July–August 2022 through a snowball sampling approach. The survey items evaluated HMPX knowledge, confidence in diagnosis and management of the disease, and the belief in conspiracies regarding emerging virus infections (EVIs). The sample size was 896 HCWs: nurses (n = 485, 54.1%), pharmacists (n = 154, 17.2%), physicians (n = 108, 12.1%), medical technicians/allied health professionals (MT/AHP, n = 96, 10.7%), and dentists (n = 53, 5.9%). An overall low level of HMPX knowledge was noticed for items assessing virus transmission and non-cutaneous symptoms of the disease, with higher knowledge among physicians. Approximately one-fifth of the study sample agreed with the false notion that HMPX is exclusive to male homosexuals (n = 183, 20.4%), which was associated with lower knowledge with higher frequency among MT/AHP compared to nurses, physicians, and pharmacists. Confidence levels were low: confidence in diagnosis based on diagnostic tests (n = 449, 50.1%), confidence in the ability to manage the HMPX (n = 426, 47.5%), and confidence in the ability to diagnose HMPX clinically (n = 289, 32.3%). Higher confidence levels were found among nurses and participants with postgraduate degrees. Higher embrace of conspiracy beliefs regarding EVIs was noticed among participants with lower knowledge, and among those who agreed or were neutral/had no opinion regarding the false idea of HMPX exclusive occurrence among male homosexuals, while lower levels of belief in conspiracies were noticed among physicians, dentists, and pharmacists compared to MT/AHP. Variable levels of HMPX knowledge were observed in this study per item, with low level of knowledge regarding virus transmission. Differences in knowledge and confidence levels in diagnosis and management of HMPX should be considered in education and training aiming to prepare for outbreak response. The relatively high prevalence of embracing conspiratorial beliefs regarding EVIs is worrisome and needs proper interventions. The attitude towards male homosexuals’ role in monkeypox spread should be evaluated in future studies considering the possibility of stigma and discrimination in this most-at-risk group.

The first imported case of monkeypox in Singapore during the 2022 outbreak – Reflections and lessons

On June 21, 2022, Singapore reported its second ever case of imported monkeypox and first linked to the ongoing multi-country outbreak that has since been declared a public health emergency of international concern. There was quick initiation of public health measures including identification and quarantine of contacts, with post-exposure smallpox vaccination.

Insights into the monkeypox virus: Making of another pandemic within the pandemic?

Just when the world started to adapt to the 'new normal' amid the coronavirus disease 19 (COVID-19) pandemic, the world is witnessing the wrath of another viral disease, the monkeypox virus (MPXV). The virus is endemic to African countries, where several outbreaks have been reported in the past. However, the present cases have been reported in non-endemic countries worldwide. Although MPX is considered to be a self-limiting disease, recent reports on its incidence have proved otherwise. The 2022 multi-country MPX outbreak has drawn the attention of global surveillance organizations and epidemiologists to trace its origin; however, there are existing gaps regarding the animal reservoirs, biological implications, and management of MPX. In view of the recent events, the World Health Organization (WHO) has also declared the ongoing MPX outbreak a global health emergency. Hence, the geographically expanding MPXV poses a significant threat to human health and public safety. In this review, the latest insights into the biology of MPXV have been provided by discussing its biological implications on human health, changing epidemiological footprint, and presently available intervention strategies. This review also sheds light on the existing lacunas and possible reasons that may have been responsible for the ongoing MPX outbreak.

Coordination and Management of COVID-19 in Africa through Health Operations and Technical Expertise Pillar: A Case Study from WHO AFRO One Year into Response.

Background: following the importation of the first Coronavirus disease 2019 (COVID-19) case into Africa on 14 February 2020 in Egypt, the World Health Organisation (WHO) regional office for Africa (AFRO) activated a three-level incident management support team (IMST), with technical pillars, to coordinate planning, implementing, supervision, and monitoring of the situation and progress of implementation as well as response to the pandemic in the region. At WHO AFRO, one of the pillars was the health operations and technical expertise (HOTE) pillar with five sub-pillars: case management, infection prevention and control, risk communication and community engagement, laboratory, and emergency medical team (EMT). This paper documents the learnings (both positive and negative for consideration of change) from the activities of the HOTE pillar and recommends future actions for improving its coordination for future emergencies, especially for multi-country outbreaks or pandemic emergency responses. Method: we conducted a document review of the HOTE pillar coordination meetings’ minutes, reports, policy and strategy documents of the activities, and outcomes and feedback on updates on the HOTE pillar given at regular intervals to the Regional IMST. In addition, key informant interviews were conducted with 14 members of the HOTE sub pillar. Key Learnings: the pandemic response revealed that shared decision making, collaborative coordination, and planning have been significant in the COVID-19 response in Africa. The HOTE pillar’s response structure contributed to attaining the IMST objectives in the African region and translated to timely support for the WHO AFRO and the member states. However, while the coordination mechanism appeared robust, some challenges included duplication of coordination efforts, communication, documentation, and information management. Recommendations: we recommend streamlining the flow of information to better understand the challenges that countries face. There is a need to define the role and responsibilities of sub-pillar team members and provide new team members with information briefs to guide them on where and how to access internal information and work under the pillar. A unified documentation system is important and could help to strengthen intra-pillar collaboration and communication. Various indicators should be developed to constantly monitor the HOTE team’s deliverables, performance and its members.

Hospitalisation for monkeypox in Milan, Italy

During the current multi-country outbreak of human monkeypox the hospitalisation rate observed in Milan, Italy was 8.8%. Bacterial superinfection and severe perianal pain were the main cause of hospitalisation requiring antibiotic treatment and analgesic therapy. One patient was treated with Cidofovir. All hospitalised patients were discharged and the outcome was favourable with full recovery.

Tecovirimat for the Treatment of Human Monkeypox: An Initial Series From Massachusetts, United States.

A large, ongoing multicountry outbreak of human monkeypox has the potential to cause considerable morbidity and mortality. Therapeutics for the treatment of smallpox, a related Orthopoxvirus, may be used and affect the natural history of monkeypox. We present 3 patients from our hospitals treated with tecovirimat, a pan-Orthopoxvirus inhibitor currently available under an expanded access investigational new drug protocol for monkeypox.

Learning from the past: the history of human monkeypox and the atypical multi-country outbreak in 2022

In 2022, the outbreak of human monkeypox (HMPX) occurred in many non-endemic countries. World Health Organization (WHO) assesses that this outbreak is "atypical". The history of monkeypox and HMPX must be reviewed to clearly recognize the "typical" outbreaks to fully understand this comment. Therefore, this paper reviews the epidemiological history of monkeypox, especially HMPX, and discusses and analyzes the atypical manifestations and the possible causes of the present outbreak based on the recent views of WHO, other organizations/institutions, and experts. The text describes the thought-provoking history of the interaction between the monkeypox virus and the human being in the past 64 years, and provides various information and views on the outbreak of HMPX, which is helpful to understand risk assessment and the potential impact of this outbreak on clinical and public health in future.