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Monkeypox is a rare disease which is rising nowadays in different countries since the first case in the UK was diagnosed on May 6, 2022, by the United Kingdom (UK) Health Security Agency. Then more than 31,000 cases were identified in over 89 countries as of August 9, 2022. In endemic areas, the monkeypox virus (MPXV) is commonly transmitted through zoonosis, while in non-endemic regions, it is spread through human-to-human transmission. Symptoms can include flu-like symptoms, rash, or sores in hands, feet, genitalia, or anus. In addition, people who did not take the smallpox vaccine were more liable to be affected than others. The exact pathogenesis and mechanisms are still unclear; however, most identified cases are reported in men who have sex with other men (MSM). According to the CDC, transmission can happen with any sexual or non-sexual contact with the infected person. However, a recent pooled meta-analysis reported that sexual contact is involved in more than 91% of the cases. Also, it is the first time that semen analysis for many patients has shown positive monkeypox virus DNA. Therefore, in this review, we will describe transmission methods for MPXV while focusing mainly on potential sexual transmission and associated sexually transmitted infections. We will also highlight the preventive measures that can limit the spread of the diseases in this regard.
Background:
Before April 2022, monkeypox virus infection in humans was seldom reported outside African regions where it is endemic. Currently, cases are occurring worldwide. Transmission, risk factors, clinical presentation, and outcomes of infection are poorly defined.
Methods:
We formed an international collaborative group of clinicians who contributed to an international case series to describe the presentation, clinical course, and outcomes of polymerase-chain-reaction-confirmed monkeypox virus infections.
Results:
We report 528 infections diagnosed between April 27 and June 24, 2022, at 43 sites in 16 countries. Overall, 98% of the persons with infection were gay or bisexual men, 75% were White, and 41% had human immunodeficiency virus infection; the median age was 38 years. Transmission was suspected to have occurred through sexual activity in 95% of the persons with infection. In this case series, 95% of the persons presented with a rash (with 64% having <10 lesions), 73% had anogenital lesions, and 41% had mucosal lesions (with 54 having a single genital lesion). Common systemic features preceding the rash included fever (62%), lethargy (41%), myalgia (31%), and headache (27%); lymphadenopathy was also common (reported in 56%). Concomitant sexually transmitted infections were reported in 109 of 377 persons (29%) who were tested. Among the 23 persons with a clear exposure history, the median incubation period was 7 days (range, 3 to 20). Monkeypox virus DNA was detected in 29 of the 32 persons in whom seminal fluid was analyzed. Antiviral treatment was given to 5% of the persons overall, and 70 (13%) were hospitalized; the reasons for hospitalization were pain management, mostly for severe anorectal pain (21 persons); soft-tissue superinfection (18); pharyngitis limiting oral intake (5); eye lesions (2); acute kidney injury (2); myocarditis (2); and infection-control purposes (13). No deaths were reported.
Conclusions:
In this case series, monkeypox manifested with a variety of dermatologic and systemic clinical findings. The simultaneous identification of cases outside areas where monkeypox has traditionally been endemic highlights the need for rapid identification and diagnosis of cases to contain further community spread.
The global vaccination programme against smallpox led to its successful eradication and averted millions of deaths. Monkeypox virus (MPXV) is a close relative of the Variola (smallpox) virus. Due to antigenic similarity, smallpox vaccines cross-protect against MPXV. However, over 70% of people living today were never vaccinated against smallpox. Symptoms of monkeypox (MPX) include fever, head- and muscle ache, lymphadenopathy and a characteristic rash that develops into papules, vesicles and pustules which eventually scab over and heal. MPX is less often fatal (case fatality rates range from <1% to up to 11%) than smallpox (up to 30%). MPXV is endemic in sub-Saharan Africa, infecting wild animals and causing zoonotic outbreaks. Exotic animal trade and international travel, combined with the increasing susceptibility of the human population due to halted vaccination, facilitated the spread of MPXV to new areas. The ongoing outbreak, with >10,000 cases in >50 countries between May and July 2022, shows that MPXV can significantly spread between people and may thus become a serious threat to public health with global consequences. Here, we summarize the current knowledge about this re-emerging virus, discuss available strategies to limit its spread and pathogenicity and evaluate its risk to the human population.
A monkeypox (MPX) outbreak has expanded worldwide since May 2022. We tested 147 clinical samples collected at different time points from 12 patients by real-time PCR. MPX DNA was detected in saliva from all cases, sometimes with high viral loads. Other samples were frequently positive: rectal swab (11/12 cases), nasopharyngeal swab (10/12 cases), semen (7/9 cases), urine (9/12 cases) and faeces (8/12 cases). These results improve knowledge on virus shedding and the possible role of bodily fluids in disease transmission.
Background
Monkeypox is a zoonotic orthopoxvirus infection endemic in central and western Africa. In May 2022, human monkeypox infections including human-to-human transmission were reported in a multi-country outbreak in Europe and North America.
Case presentations
Here we present the first two cases of monkeypox infection in humans diagnosed in Germany. We present clinical and virological findings, including the detection of monkeypox virus DNA in blood and semen. The clinical presentation and medical history of our patients suggest close physical contact during sexual interactions as the route of infection.
Conclusion
Monkeypox requires rapid diagnosis and prompt public health response. The disease should be considered in the current situation especially the differential diagnosis of vesicular or pustular rash, particularly in patients with frequent sexual contacts. Most importantly, it is essential to raise awareness among all health professionals for the rapid and correct recognition and diagnosis of this disease, which is probably still underreported in Europe (Adler et al. in Lancet Infect Dis https://doi.org/10.1016/s1473-3099(22)00228-6, 2022).
Up to 22 June 2022, 508 confirmed cases of monkeypox (MPX) have been reported in the Madrid region of Spain, 99% are men (n = 503) with a median age of 35 years (range: 18–67). In this ongoing outbreak, 427 cases (84.1%) reported condomless sex or sex with multiple partners within the 21 days before onset of symptoms, who were predominantly men who have sex with men (MSM) (n = 397; 93%). Both the location of the rash, mainly in the anogenital and perineal area, as well as the presence of inguinal lymphadenopathy suggest that close physical contact during sexual activity played a key role in transmission. Several cases reported being at a sauna in the city of Madrid (n = 34) or a mass event held on the Spanish island of Gran Canaria (n = 27), activities which may represent a conducive environment for MPX virus spread, with many private parties also playing an important role. Because of the rapid implementation of MPX surveillance in Madrid, one of the largest outbreaks reported outside Africa was identified. To minimise transmission, we continue to actively work with LGBTIQ+ groups and associations, with the aim of raising awareness among people at risk and encouraging them to adopt preventive measures.
As the fear of the coronavirus disease 2019 (COVID-19) pandemic subsides, countries around the globe are now dealing with a fear of the epidemic surrounding the prevalence of monkeypox cases in various regions. Previously endemic to regions of Africa, the majority of monkeypox cases associated with the 2022 outbreak are being noted in countries around Europe and in the western hemisphere. While contact-tracing projects are being conducted by various organizations, it is unknown how this outbreak began. Monkeypox virus is one of the many zoonotic viruses that belong to the Orthopoxvirus genus of the Poxviridae family. Monkeypox cases received global attention during the 1970s, after the global eradication of smallpox. The smallpox vaccine provided cross-immunity to the monkeypox virus. Upon the cessation of smallpox vaccine administration, monkeypox cases became more prevalent. It was not until the 2003 US outbreak that monkeypox truly gained global attention. Despite the virus being named monkeypox, monkeys are not the origin of the virus. Several rodents and small mammals have been attributed as the source of the virus; however, it is unknown what the true origin of monkeypox is. The name monkeypox is due to the viral infection being first witnessed in macaque monkeys. Though human-to-human transmission of monkeypox is very rare, it is commonly attributed to respiratory droplets or direct contact with mucocutaneous lesions of an infected individual. Currently, there is no treatment allocated for infected individuals, however, supportive treatments can be administered to provide symptom relief to individuals; Medications such as tecovirimat may be administered in very severe cases. These treatments are subjective, as there are no exact guidelines for symptom relief.
The largest monkeypox virus (MPXV) outbreak described so far in non-endemic countries was identified in May 20221-6. Here, shotgun metagenomics allowed the rapid reconstruction and phylogenomic characterization of the first MPXV outbreak genome sequences, showing that this MPXV belongs to clade 3 and that the outbreak most likely has a single origin. Although 2022 MPXV (lineage B.1) clustered with 2018-2019 cases linked to an endemic country, it segregates in a divergent phylogenetic branch, likely reflecting continuous accelerated evolution. An in-depth mutational analysis suggests the action of host APOBEC3 in viral evolution as well as signs of potential MPXV human adaptation in ongoing microevolution. Our findings also indicate that genome sequencing may provide resolution to track the spread and transmission of this presumably slow-evolving dsDNA virus.
Since May 2022, an outbreak of monkeypox has been ongoing in non-endemic countries. We report four cases in Italy in young adult men reporting condomless sexual intercourse. The patients are in good clinical condition with no need for specific antiviral drugs. Biological samples from seminal fluid were positive for monkeypox viral DNA. For many other viruses found in semen there is no evidence of sexual transmission. The possibility of sexual transmission of monkeypox virus needs to be investigated.
Background
Cases of human monkeypox are rarely seen outside of west and central Africa. There are few data regarding viral kinetics or the duration of viral shedding and no licensed treatments. Two oral drugs, brincidofovir and tecovirimat, have been approved for treatment of smallpox and have demonstrated efficacy against monkeypox in animals. Our aim was to describe the longitudinal clinical course of monkeypox in a high-income setting, coupled with viral dynamics, and any adverse events related to novel antiviral therapies.
Methods
In this retrospective observational study, we report the clinical features, longitudinal virological findings, and response to off-label antivirals in seven patients with monkeypox who were diagnosed in the UK between 2018 and 2021, identified through retrospective case-note review. This study included all patients who were managed in dedicated high consequence infectious diseases (HCID) centres in Liverpool, London, and Newcastle, coordinated via a national HCID network.
Findings
We reviewed all cases since the inception of the HCID (airborne) network between Aug 15, 2018, and Sept 10, 2021, identifying seven patients. Of the seven patients, four were men and three were women. Three acquired monkeypox in the UK: one patient was a health-care worker who acquired the virus nosocomially, and one patient who acquired the virus abroad transmitted it to an adult and child within their household cluster. Notable disease features included viraemia, prolonged monkeypox virus DNA detection in upper respiratory tract swabs, reactive low mood, and one patient had a monkeypox virus PCR-positive deep tissue abscess. Five patients spent more than 3 weeks (range 22–39 days) in isolation due to prolonged PCR positivity. Three patients were treated with brincidofovir (200 mg once a week orally), all of whom developed elevated liver enzymes resulting in cessation of therapy. One patient was treated with tecovirimat (200mg twice daily for 2 weeks orally), experienced no adverse effects, and had a shorter duration of viral shedding and illness (10 days hospitalisation) compared with the other six patients. One patient experienced a mild relapse 6 weeks after hospital discharge.
Interpretation
Human monkeypox poses unique challenges, even to well resourced health-care systems with HCID networks. Prolonged upper respiratory tract viral DNA shedding after skin lesion resolution challenged current infection prevention and control guidance. There is an urgent need for prospective studies of antivirals for this disease.
Funding
None.
Monkeypox, a zoonotic disease caused by an orthopoxvirus, results in a smallpox-like disease in humans. Since monkeypox in humans was initially diagnosed in 1970 in the Democratic Republic of the Congo (DRC), it has spread to other regions of Africa (primarily West and Central), and cases outside Africa have emerged in recent years. We conducted a systematic review of peer-reviewed and grey literature on how monkeypox epidemiology has evolved, with particular emphasis on the number of confirmed, probable, and/or possible cases, age at presentation, mortality, and geographical spread. The review is registered with PROSPERO (CRD42020208269). We identified 48 peer-reviewed articles and 18 grey literature sources for data extraction. The number of human monkeypox cases has been on the rise since the 1970s, with the most dramatic increases occurring in the DRC. The median age at presentation has increased from 4 (1970s) to 21 years (2010–2019). There was an overall case fatality rate of 8.7%, with a significant difference between clades—Central African 10.6% (95% CI: 8.4%– 13.3%) vs. West African 3.6% (95% CI: 1.7%– 6.8%). Since 2003, import- and travel-related spread outside of Africa has occasionally resulted in outbreaks. Interactions/activities with infected animals or individuals are risk behaviors associated with acquiring monkeypox. Our review shows an escalation of monkeypox cases, especially in the highly endemic DRC, a spread to other countries, and a growing median age from young children to young adults. These findings may be related to the cessation of smallpox vaccination, which provided some cross-protection against monkeypox, leading to increased human-to-human transmission. The appearance of outbreaks beyond Africa highlights the global relevance of the disease. Increased surveillance and detection of monkeypox cases are essential tools for understanding the continuously changing epidemiology of this resurging disease.
The aim of this study was to systematically review the literature investigating the physical demands of sexual intercourse and to synthesize the evidence related to this research topic. Original studies published on PubMed, Scopus, and Web of Science up until April 2020 were examined. The Effective Public Health Practice Project scale was used to assess the methodological quality of each study. Eighteen studies analyzed physical demands during sexual intercourse through the physiological demands (n = 14) and kinematics (n = 4) of sexual intercourse. Sexual intercourse can elicit an energy expenditure of ~ 100 kcal (or ~ 6 metabolic equivalent units, METs) during the activity, mean heart rates between ~ 90 and ~ 130 beats per minute (bpm), and peak heart rates up to ~ 170 bpm. However, these physical demands may vary depending on health status, intercourse position, activity duration, intercourse phase, and sex differences. The movement pattern was cyclic in all positions and the greatest demands in lumbar spine flexion were found in the missionary positions for women. Missionary and side-lying positions elicited the greatest lumbar flexion movement in men. Regarding the movement of the hip joint during sexual intercourse, flexion, abduction, and external rotation mainly characterized the woman’s movement while external rotation did so in the man. In conclusion, sexual intercourse may elicit moderate intensity physical demands, but these demands vary depending on contextual variables. In addition, not only studies combining physiological and kinematic analyses are necessary but also more high-quality studies need to be published in order to have a better understanding of the physical demands of sexual intercourse.
Monkeypox is a zoonotic disease caused by monkeypox virus (MPXV), which is a member of orthopoxvirus genus. The reemergence of MPXV in 2017 (at Bayelsa state) after 39 years of no reported case in Nigeria, and the export of travelers' monkeypox (MPX) from Nigeria to other parts of the world, in 2018 and 2019, respectively, have raised concern that MPXV may have emerged to occupy the ecological and immunological niche vacated by smallpox virus. This review X-rays the current state of knowledge pertaining the infection biology, epidemiology, and evolution of MPXV in Nigeria and worldwide, especially with regard to the human, cellular, and viral factors that modulate the virus transmission dynamics, infection, and its maintenance in nature. This paper also elucidates the role of recombination, gene loss and gene gain in MPXV evolution, chronicles the role of signaling in MPXV infection, and reviews the current therapeutic options available for the treatment and prevention of MPX. Additionally, genome-wide phylogenetic analysis was undertaken, and we show that MPXV isolates from recent 2017 outbreak in Nigeria were monophyletic with the isolate exported to Israel from Nigeria but do not share the most recent common ancestor with isolates obtained from earlier outbreaks, in 1971 and 1978, respectively. Finally, the review highlighted gaps in knowledge particularly the non-identification of a definitive reservoir host animal for MPXV and proposed future research endeavors to address the unresolved questions.
In May 2019, we investigated monkeypox in a traveler from Nigeria to Singapore. The public health response included rapid identification of contacts, use of quarantine, and postexposure smallpox vaccination. No secondary cases were identified. Countries should develop surveillance systems to detect emerging infectious diseases globally.
Monkeypox is a vesicular-pustular illness that carries a secondary attack rate in the order of 10% in contacts unvaccinated against smallpox. Case fatality rates range from 1 to 11%, but scarring and other sequelae are common in survivors. It continues to cause outbreaks in remote populations in Central and West Africa, in areas with poor access and weakened or disrupted surveillance capacity and information networks. Recent outbreaks in Nigeria (2017-18) and Cameroon (2018) have occurred where monkeypox has not been reported for over 20 years. This has prompted concerns over whether there have been changes in the biology and epidemiology of the disease that may in turn have implications for how outbreaks and cases should best be managed. A systematic review was carried out to examine reported data on human monkeypox outbreaks over time, and to identify if and how epidemiology has changed. Published and grey literature were critically analysed, and data extracted to inform recommendations on outbreak response, use of case definitions and public health advice. The level of detail, validity of data, geographical coverage and consistency of reporting varied considerably across the 71 monkeypox outbreak documents obtained. An increase in cases reported over time was supported by literature from the Democratic Republic of Congo (DRC). Data were insufficient to measure trends in secondary attack rates and case fatality rates. Phylogenetic analyses consistently identify two strains of the virus without evidence of emergence of a new strain. Understanding of monkeypox virulence with regard to clinical presentation by strain is minimal, with infrequent sample collection and laboratory analysis. A variety of clinical and surveillance case definitions are described in the literature: two definitions have been formally evaluated and showed high sensitivity but low specificity. These were specific to a Congo-Basin (CB) strain–affected area of the DRC where they were used. Evidence on use of antibiotics for prophylaxis against secondary cutaneous infection is anecdotal and limited. Current evidence suggests there has been an increase in total monkeypox cases reported by year in the DRC irrespective of advancements in the national Integrated Disease Surveillance and Response (IDSR) system. There has been a marked increase in number of individual monkeypox outbreak reports, from outside the DRC in between 2010 and 2018, particularly in the Central African Republic (CAR) although this does not necessarily indicate an increase in annual cases over time in these areas. The geographical pattern reported in the Nigeria outbreak suggests a possible new and widespread zoonotic reservoir requiring further investigation and research. With regards to outbreak response, increased attention is warranted for high-risk patient groups, and nosocomial transmission risks. The animal reservoir remains unknown and there is a dearth of literature informing case management and successful outbreak response strategies. Up-to-date complete, consistent and longer-term research is sorely needed to inform and guide evidence-based response and management of monkeypox outbreaks.
We report a case of monkeypox in a man who returned from Nigeria to Israel in 2018. Virus was detected in pustule swabs by transmission electron microscopy and PCR and confirmed by immunofluorescence assay, tissue culture, and ELISA. The West Africa monkeypox outbreak calls for increased awareness by public health authorities worldwide.
Background
In September 2017, Nigeria experienced a large outbreak of human monkeypox (HMPX). In this study, we report the outbreak experience and response in the Niger Delta University Teaching Hospital (NDUTH), Bayelsa state, where the index case and majority of suspected cases were reported.
Methods
In a cross-sectional study between September 25th and 31st December 2017, we reviewed the clinical and laboratory characteristics of all suspected and confirmed cases of HMPX seen at the NDUTH and appraised the plans, activities and challenges of the hospital in response to the outbreak based on documented observations of the hospital’s infection control committee (IPC). Monkeypox cases were defined using the interim national guidelines as provided by the Nigerian Centre for Disease Control (NCDC).
Results
Of 38 suspected cases of HMPX, 18(47.4%) were laboratory confirmed, 3(7.9%) were probable, while 17 (18.4%) did not fit the case definition for HMPX. Majority of the confirmed/probable cases were adults (80.9%) and males (80.9%). There was concomitant chicken pox, syphilis and HIV-1 infections in two confirmed cases and a case of nosocomial infection in one healthcare worker (HCW). The hospital established a make-shift isolation ward for case management, constituted a HMPX response team and provided IPC resources. At the outset, some HCWs were reluctant to participate in the outbreak and others avoided suspected patients. Some patients and their family members experienced stigma and discrimination and there were cases of refusal of isolation. Repeated trainings and collaborative efforts by all stakeholders addressed some of these challenges and eventually led to successful containment of the outbreak.
Conclusion
While the 2017 outbreak of human monkeypox in Nigeria was contained, our report reveals gaps in outbreak response that could serve as lessons to other hospitals to strengthen epidemic preparedness and response activities in the hospital setting.
In early September 2018, two cases of monkeypox were reported in the United Kingdom (UK), diagnosed on 7 September in Cornwall (South West England) and 11 September in Blackpool (North West England). The cases were epidemiologically unconnected and had recently travelled to the UK from Nigeria, where monkeypox is currently circulating. We describe the epidemiology and the public health response for the first diagnosed cases outside the African continent since 2003.
Virus purification in a high-containment setting provides unique challenges due to barrier precautions and operational safety approaches that are not necessary in lower biosafety level (BSL) 2 environments. The need for high risk group pathogen diagnostic assay development, anti-viral research, pathogenesis and vaccine efficacy research necessitates work in BSL-3 and BSL-4 labs with infectious agents. When this work is performed in accordance with BSL-4 practices, modifications are often required in standard protocols. Classical virus purification techniques are difficult to execute in a BSL-3 or BSL-4 laboratory because of the work practices used in these environments. Orthopoxviruses are a family of viruses that, in some cases, requires work in a high-containment laboratory and due to size do not lend themselves to simpler purification methods. Current CDC purification techniques of orthopoxviruses uses 1,1,2-trichlorotrifluoroethane, commonly known as Genetron®. Genetron® is a chlorofluorocarbon (CFC) that has been shown to be detrimental to the ozone and has been phased out and the limited amount of product makes it no longer a feasible option for poxvirus purification purposes. Here we demonstrate a new orthopoxvirus purification method that is suitable for high-containment laboratories and produces virus that is not only comparable to previous purification methods, but improves on purity and yield.
These guidelines provide updated, GRADE-based recommendations on the use of vaccines in HIVpositive adults. Several factors have made the updating of HIV-specific vaccination guidelines important: effective antiretroviral therapy (ART) has substantially modified the natural history of HIV infection, vaccination practices are evolving, and a large number of novel vaccines are becoming available in clinical care. The update contains important new guidance regarding the use of new vaccines against human papillomavirus (HPV), shingles (herpes zoster), and pneumococcus. Further key updates are related to the use of hepatitis B, meningococcus, and pertussis vaccines. Compared with HIV-negative individuals, HIV-positive adults often have an increased risk of infection or experience more severe morbidity following exposure to vaccine-preventable diseases, and therefore a lower threshold for extending indications and offering vaccination may be appropriate relative to the general population. Improved health and prognosis mean that HIV-positive adults are also increasingly likely to engage in travel or occupations that carry a risk of exposure to infectious agents, and these otherwise healthy individuals should not be denied protection or engagement with such activities if evidence indicates vaccination is safe and immunogenic. Immune responses to vaccination are often sub-optimal in HIV-positive patients, and while these improve with ART, they often remain lower and decline more rapidly than in HIV-negative individuals. However, many of these vaccines still afford protection and for some vaccines it is possible to improve immunogenicity by offering modified vaccine schedules, with higher or more frequent doses, without compromising safety. Non-replicating vaccines (e.g., whole inactivated, polysaccharide, conjugated, and subunit vaccines, or virus-like particles) can be used safely in HIV-positive persons, whereas replicating (live) vaccines have traditionally been contraindicated. However, ART-induced Immunorestoration reduces the risk of adverse events, in many cases shifting the risk-benefit ratio in favour of vaccination, whereby the risk of disease with natural infection becomes greater than the risk of live vaccine-related adverse events. Important examples of replicating vaccines that can be used in HIV-positive persons with good immunity include those for measles, mumps and rubella (MMR), varicella-zoster virus (VZV), and yellow fever. For vaccinated individuals, the importance of infection avoidance and infection control should continue to be emphasised. It is envisaged that the HIV specialist should provide overall guidance on vaccine use and enlist the help of primary care physicians for vaccine administration. Education of health care providers and good communication are key requirements to ensure successful implementation of this guidance. Despite evidence that HIV-positive persons benefit from vaccination, there are persisting perceptions about disease incidence and burden, and vaccine effectiveness and safety, which affect vaccination practices among health professionals caring for HIV-positive patients. It is hoped that this guidance will help overcoming such barriers.
A 600-fold increase in monkeypox cases occurred in the Bokungu Health Zone of the Democratic Republic of the Congo during the second half of 2013; this increase prompted an outbreak investigation. A total of 104 possible cases were reported from this health zone; among 60 suspected cases that were tested, 50 (48.1%) cases were confirmed by laboratory testing, and 10 (9.6%) tested negative for monkeypox virus (MPXV) infection. The household attack rate (i.e., rate of persons living with an infected person that develop symptoms of MPXV infection) was 50%. Nine families showed >1 transmission event, and >6 transmission events occurred within this health zone. Mean incubation period was 8 days (range 4-14 days). The high attack rate and transmission observed in this study reinforce the importance of surveillance and rapid identification of monkeypox cases. Community education and training are needed to prevent transmission of MPXV infection during outbreaks.
In 2014, CDC published updated guidelines for the prevention and treatment of anthrax (Hendricks KA, Wright ME, Shadomy SV et al. Centers for Disease Control and Prevention expert panel meetings on prevention and treatment of anthrax in adults. Emerg Infect Dis 2014;20[2] Available at http://wwwnc.cdc.gov/eid/article/20/2/13-0687_article.htm). These guidelines provided recommended best practices for the diagnosis and treatment of persons with naturally occurring or bioterrorism-related anthrax in conventional medical settings. An aerosolized release of Bacillus anthracis spores over densely populated areas could become a mass-casualty incident. To prepare for this possibility, the US. government has stockpiled equipment and therapeutics (known as medical countermeasures [MCMs]) for anthrax prevention and treatment. However, previously developed publicly available clinical recommendations have not addressed the use of MCMs or clinical management during an anthrax mass-casualty incident, when the number of patients is likely to exceed the ability of the health care infrastructure to provide conventional standards of care and supplies of MCMs might be inadequate to meet the demand required. To address this gap, in 2013, CDC conducted a series of systematic reviews of the scientific literature on anthrax to identify evidence that could help clinicians and public health authorities set guidelines for intravenous antimicrobial and antitoxin use, diagnosis of anthrax meningitis, and management of common anthrax-specific complications in the setting of a mass-casualty incident. Evidence from these reviews was presented to professionals with expertise in anthrax, critical care, and disaster medicine during a series of workgroup meetings that were held from August 2013 through March 2014. In March 2014, a meeting was held at which 102 subject matter experts discussed the evidence and adapted the existing best practices guidance to a clinical use framework for the judicious, efficient, and rational use of stockpiled MCMs for the treatment of anthrax during a mass-casualty incident, which is described in this report. This report addresses elements of hospital-based acute care, specifically antitoxins and intravenous antimicrobial use, and the diagnosis and management of common anthrax-specific complications during a mass-casualty incident. The recommendations in this report should be implemented only after predefined triggers have been met for shifting from conventional to contingency or crisis standards of care, such as when the magnitude of cases might lead to impending shortages of intravenous antimicrobials, antitoxins, critical care resources (e.g., chest tubes and chest drainage systems), or diagnostic capability. This guidance does not address prima?), triage decisions, anthrax postexposure prophylaxis, hospital bed or workforce surge capacity, or the logistics of dispensing MCMs. Clinicians, hospital administrators, state and local health officials, and planners can use these recommendations to assist in the development of crisis protocols that will ensure national preparedness for an anthrax mass-casualty incident.
Human monkeypox is a viral zoonosis caused by monkeypox virus, an orthopoxvirus (OPXV). The majority of human monkeypox cases have been reported in moist forested regions in West and Central Africa, particularly in the Democratic Republic of the Congo (DRC). In this study we investigated zoonotic OPXV infection among wild animals in Zambia, which shares a border with DRC, to assess geographical distribution of OPXV. We screened for OPXV antibodies in sera from non-human primates (NHPs), rodents, and shrews by ELISA, and performed real-time PCR to detect OPXV DNA in spleen samples. Serological analysis indicated that 38 of 259 (14.7%) rodents, 14 of 42 (33.3%) shrews, and four of 188 (2.1%) NHPs had antibodies against OPXV. The OPXV DNA could not be detected in spleens from any animals tested. Our results indicated that wild animals living in rural human habitation areas of Zambia have been infected with OPXV.
For many infectious disease processes such as emerging zoonoses and vaccine-preventable diseases, [Formula: see text] and infections occur as self-limited stuttering transmission chains. A mechanistic understanding of transmission is essential for characterizing the risk of emerging diseases and monitoring spatio-temporal dynamics. Thus methods for inferring [Formula: see text] and the degree of heterogeneity in transmission from stuttering chain data have important applications in disease surveillance and management. Previous researchers have used chain size distributions to infer [Formula: see text], but estimation of the degree of individual-level variation in infectiousness (as quantified by the dispersion parameter, [Formula: see text]) has typically required contact tracing data. Utilizing branching process theory along with a negative binomial offspring distribution, we demonstrate how maximum likelihood estimation can be applied to chain size data to infer both [Formula: see text] and the dispersion parameter that characterizes heterogeneity. While the maximum likelihood value for [Formula: see text] is a simple function of the average chain size, the associated confidence intervals are dependent on the inferred degree of transmission heterogeneity. As demonstrated for monkeypox data from the Democratic Republic of Congo, this impacts when a statistically significant change in [Formula: see text] is detectable. In addition, by allowing for superspreading events, inference of [Formula: see text] shifts the threshold above which a transmission chain should be considered anomalously large for a given value of [Formula: see text] (thus reducing the probability of false alarms about pathogen adaptation). Our analysis of monkeypox also clarifies the various ways that imperfect observation can impact inference of transmission parameters, and highlights the need to quantitatively evaluate whether observation is likely to significantly bias results.
ABSTRACT:
Orthopoxviruses, including variola virus, vaccinia virus, and monkeypox virus, have previously been documented in humans in West Africa, however, no cases of human orthopoxvirus infection have been reported in the region since 1986. We conducted a serosurvey to determine whether human exposure to orthopoxviruses continues to occur in eastern Sierra Leone.
To examine evidence of exposure to orthopoxviruses in the Kenema District of Sierra Leone, we collected and tested sera from 1596 persons by IgG ELISA and a subset of 313 by IgM capture ELISA. Eleven persons born after the cessation of smallpox vaccination had high orthopoxvirus-specific IgG values, and an additional 6 persons had positive IgM responses. No geographic clustering was noted.
These data suggest that orthopoxviruses continue to circulate in Sierra Leone. Studies aimed at obtaining orthopoxvirus isolates and/or genetic sequences from rodents and symptomatic humans in the area are indicated.
Human monkeypox has never been reported in Ghana, but rodents captured in forested areas of southern Ghana were the source of the monkeypox virus introduced into the United States in 2003. Subsequent to the outbreak in the United States, 204 animals were collected from two commercial trapping sites in Ghana. Animal tissues were examined for the presence of orthopoxvirus (OPXV) DNA using a real-time polymerase chain reaction, and sera were assayed for antibodies against OPXV. Animals from five genera (Cricetomys, Graphiurus, Funiscirus, and Heliosciurus) had antibodies against OPXV, and three genera (Cricetomys, Graphiurus, and Xerus) had evidence of OPXV DNA in tissues. Additionally, 172 persons living near the trapping sites were interviewed regarding risk factors for OPXV exposure, and their sera were analyzed. Fifty-three percent had IgG against OPXV; none had IgM. Our findings suggest that several species of forest-dwelling rodents from Ghana are susceptible to naturally occurring OPXV infection, and that persons living near forests may have low-level or indirect exposure to OPXV-infected animals, possibly resulting in sub-clinical infections.
During May and June 2003, an outbreak of febrile illness with vesiculopustular eruptions occurred among persons in the midwestern United States who had had contact with ill pet prairie dogs obtained through a common distributor. Zoonotic transmission of a bacterial or viral pathogen was suspected.
We reviewed medical records, conducted interviews and examinations, and collected blood and tissue samples for analysis from 11 patients and one prairie dog. Histopathological and electron-microscopical examinations, microbiologic cultures, and molecular assays were performed to identify the etiologic agent.
The initial Wisconsin cases evaluated in this outbreak occurred in five males and six females ranging in age from 3 to 43 years. All patients reported having direct contact with ill prairie dogs before experiencing a febrile illness with skin eruptions. We found immunohistochemical or ultrastructural evidence of poxvirus infection in skin-lesion tissue from four patients. Monkeypox virus was recovered in cell cultures of seven samples from patients and from the prairie dog. The virus was identified by detection of monkeypox-specific DNA sequences in tissues or isolates from six patients and the prairie dog. Epidemiologic investigation suggested that the prairie dogs had been exposed to at least one species of rodent recently imported into the United States from West Africa.
Our investigation documents the isolation and identification of monkeypox virus from humans in the Western Hemisphere. Infection of humans was associated with direct contact with ill prairie dogs that were being kept or sold as pets.
Despite the success of the WHO-led smallpox eradication programme a quarter of a century ago, there remains considerable fear that variola virus, or other related pathogenic poxviruses such as monkeypox, could re-emerge and spread disease in the human population. Even today, we are still mostly ignorant about why most poxvirus infections of vertebrate hosts show strict species specificity, or how zoonotic poxvirus infections occur when poxviruses occasionally leap into novel host species. Poxvirus tropism at the cellular level seems to be regulated by intracellular events downstream of virus binding and entry, rather than at the level of specific host receptors as is the case for many other viruses. This review summarizes our current understanding of poxvirus tropism and host range, and discusses the prospects of exploiting host-restricted poxvirus vectors for vaccines, gene therapy or tissue-targeted oncolytic viral therapies for the treatment of human cancers.
Background:
In spring of 2022, an outbreak of monkeypox (mpox) spread worldwide. Here, we describe performance characteristics of monkeypox virus (MPXV)-specific and pan-orthopoxvirus qPCR assays for clinical use.
Methods:
We validated probe-based qPCR assays targeting MPXV-specific loci F3L and G2R (genes MPXVgp052/OPG065 and MPXVgp002 and gp190/OPG002, respectively) and a pan-orthopoxvirus assay targeting the E9L locus (MPXVgp057/OPG071). Clinical samples and synthetic controls were extracted using the Roche MP96 or Promega Maxwell 48 instrument. qPCR was performed on the AB7500 thermocycler. Synthetic control DNA and high concentration clinical samples were quantified by droplet PCR. Cross-reactivity was evaluated for camelpox and cowpox genomic DNA, vaccinia culture supernatant, and HSV- and VZV-positive clinical specimens. We also tested the performance of the F3L assay using dry swabs, Aptima vaginal and rectal swabs, nasopharyngeal, rectal, and oral swabs, cerebrospinal fluid, plasma, serum, whole blood, breastmilk, urine, saliva, and semen.
Results:
The MPXV-F3L assay is reproducible at a limit of detection (LoD) of 65.6 copies/mL of viral DNA in viral transport medium/universal transport medium (VTM/UTM), or 3.3 copies/PCR reaction. No cross-reactivity with herpesviruses or other poxviruses was observed. MPXV-F3L detects MPXV DNA in alternative specimen types, with an LoD ranging between 260-1000 copies/mL, or 5.7-10 copies/PCR reaction. In clinical swab VTM specimens, MPXV-F3L and MPXV-G2R assays outperformed OPXV-E9L by an average of 2.4 and 2.8 Cts, respectively. MPXV-G2R outperformed MPXV-F3L by 0.4 Cts, consistent with presence of two copies of G2R present in labile inverted terminal repeats (ITRs) of MPXV genome.
Conclusions:
MPXV is readily detected by qPCR using three clinically validated assays.
Background: Human monkeypox (HMPX) is currently spreading outside endemic countries in Africa and the majority of those affected are gay and bisexual men within interconnected sexual networks. We investigated the sexual history of HMPX cases seen at a tertiary hospital in Bayelsa State during the 2017–2018 outbreak in Nigeria.
Method: A cross-sectional study was conducted between 20 October 2017 and 2 January 2019 among adult confirmed/probable HMPX cases. A questionnaire was used to collect data on the sexual history of participants, including sexual contact in relation to the first symptom, and high-risk behaviours (HRB) such as a history of condomless casual sex, multiple sexual partners, and transactional sex.
Results: Of 21 patients, 16 (76.2%) gave consent to participate in the study: age range of 22–43 years, 75% males, three (18.8%) HIV-1 positive, and 13 (81.2%) with genital ulcers. Nine (56.2%) of participants reported HRB, and all were male heterosexuals. Eight of the 16 participants (50%) reported having sex within a month before their first symptom, and five (62.5%) of this number reported HRB. There were two cases of sex with a partner with a non-genital rash, and a spouse who developed a vulval ulcer four days after sex with her husband.
Conclusion: Our results support the role of sexual contact in the transmission of monkeypox among some confirmed cases from Nigeria. However, future elaborate studies are required to confirm if sexual behaviour and sexual transmission are associated with HMPX in Nigeria.
Background:
Historically, human monkeypox virus cases in the UK have been limited to imported infections from west Africa. Currently, the UK and several other countries are reporting a rapid increase in monkeypox cases among individuals attending sexual health clinics, with no apparent epidemiological links to endemic areas. We describe demographic and clinical characteristics of patients diagnosed with human monkeypox virus attending a sexual health centre.
Methods:
In this observational analysis, we considered patients with confirmed monkeypox virus infection via PCR detection attending open-access sexual health clinics in London, UK, between May 14 and May 25, 2022. We report hospital admissions and concurrent sexually transmitted infection (STI) proportions, and describe our local response within the first 2 weeks of the outbreak.
Findings:
Monkeypox virus infection was confirmed in 54 individuals, all identifying as men who have sex with men (MSM), with a median age of 41 years (IQR 34-45). 38 (70%) of 54 individuals were White, 26 (48%) were born in the UK, and 13 (24%) were living with HIV. 36 (67%) of 54 individuals reported fatigue or lethargy, 31 (57%) reported fever, and ten (18%) had no prodromal symptoms. All patients presented with skin lesions, of which 51 (94%) were anogenital. 37 (89%) of 54 individuals had skin lesions affecting more than one anatomical site and four (7%) had oropharyngeal lesions. 30 (55%) of 54 individuals had lymphadenopathy. One in four patients had a concurrent STI. Five (9%) of 54 individuals required admission to hospital, mainly due to pain or localised bacterial cellulitis requiring antibiotic intervention or analgesia. We recorded no fatal outcomes.
Interpretation:
Autochthonous community monkeypox virus transmission is currently observed among MSM in the UK. We found a high proportion of concomitant STIs and frequent anogenital symptoms, suggesting transmissibility through local inoculation during close skin-to-skin or mucosal contact, during sexual activity. Additional resources are required to support sexual health and other specialist services in managing this condition. A review of the case definition and better understanding of viral transmission routes are needed to shape infection control policies, education and prevention strategies, and contact tracing.
Funding:
None.
Following two reports of monkeypox virus infection in individuals who returned from Nigeria to the USA, one who returned to Texas (July 2021) and the other to the Washington, DC area (November 2021), the number of monkeypox infection have dramatically increased. This sounded an alarm of potential for spreading of the virus throughout the USA. During 2022, there was a report of monkeypox virus infection (May 6, 2022) in a British national following a visit to Nigeria who developed readily recognizable signs and symptoms of monkeypox virus infection. Soon following this report, case numbers climbed. By June 10, 2022, more than 1,500 cases were reported in 43 countries, including Europe and North America. While the prevalence of the monkeypox virus is well known in central and western Africa, its presence in the developed world has raised disturbing signs for worldwide spread. While infection was reported during the past half-century, starting in the Democratic Republic of Congo in 1970, in the United States, only sporadic monkeypox cases have been reported. All cases have been linked to international travel or through African animal imports. The monkeypox virus is transmitted through contact with infected skin, body fluids, or respiratory droplets. The virus spreads from oral and nasopharyngeal fluid exchanges or by intradermal injection; then rapidly replicates at the inoculation site with spreads to adjacent lymph nodes. Monkeypox disease begins with constitutional symptoms that include fever, chills, headache, muscle aches, backache, and fatigue. Phylogenetically the virus has two clades. One clade emerged from West Africa and the other in the Congo Basin of Central Africa. During the most recent outbreak, the identity of the reservoir host or the primary carriage remains unknown. African rodents are the suspected intermediate hosts. At the same time, the Centers for Disease Control (CDC) affirmed that there are no specific treatments for the 2022 monkeypox virus infection; existing antivirals shown to be effective against smallpox may slow monkeypox spread. A smallpox vaccine JYNNEOS (Imvamune or Imvanex) may also be used to prevent infection. The World Health Organization (WHO), has warned that the world could be facing a formidable infectious disease challenge in light of the current status of worldwide affairs. These affairs include the SARS-COVID-19 pandemic and the Ukraine-Russia war. In addition, the recent rise in case of numbers worldwide could continue to pose an international threat. With this in mind, strategies to mitigate the spread of monkeypox virus are warranted.
The once slow spreading virus may have found a new niche in tightly connected sexual networks
Human respiratory virus infections lead to a spectrum of respiratory symptoms and disease severity, contributing to substantial morbidity, mortality and economic losses worldwide, as seen in the COVID-19 pandemic. Belonging to diverse families, respiratory viruses differ in how easy they spread (transmissibility) and the mechanism (modes) of transmission. Transmissibility as estimated by the basic reproduction number (R0) or secondary attack rate is heterogeneous for the same virus. Respiratory viruses can be transmitted via four major modes of transmission: direct (physical) contact, indirect contact (fomite), (large) droplets and (fine) aerosols. We know little about the relative contribution of each mode to the transmission of a particular virus in different settings, and how its variation affects transmissibility and transmission dynamics. Discussion on the particle size threshold between droplets and aerosols and the importance of aerosol transmission for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza virus is ongoing. Mechanistic evidence supports the efficacies of non-pharmaceutical interventions with regard to virus reduction; however, more data are needed on their effectiveness in reducing transmission. Understanding the relative contribution of different modes to transmission is crucial to inform the effectiveness of non-pharmaceutical interventions in the population. Intervening against multiple modes of transmission should be more effective than acting on a single mode.
Recently, concern has been raised about the emergence of human monkeypox virus and the occasionally severe clinical presentation bearing resemblance to that of smallpox. In 2018 3 patients in the UK were diagnosed with monkeypox, and the frequency and geographic distribution of cases across West and Central Africa have increased in recent years. In Nigeria, most monkeypox patients are aged <40 years and lack cross-protective immunity because they were born after discontinuation of the smallpox eradication campaign. This article reviews the epidemiology, clinical features, and management of monkeypox and discusses its growing public health threat in this context.
Background:
In September, 2017, human monkeypox re-emerged in Nigeria, 39 years after the last reported case. We aimed to describe the clinical and epidemiological features of the 2017-18 human monkeypox outbreak in Nigeria.
Methods:
We reviewed the epidemiological and clinical characteristics of cases of human monkeypox that occurred between Sept 22, 2017, and Sept 16, 2018. Data were collected with a standardised case investigation form, with a case definition of human monkeypox that was based on previously established guidelines. Diagnosis was confirmed by viral identification with real-time PCR and by detection of positive anti-orthopoxvirus IgM antibodies. Whole-genome sequencing was done for seven cases. Haplotype analysis results, genetic distance data, and epidemiological data were used to infer a likely series of events for potential human-to-human transmission of the west African clade of monkeypox virus.
Findings:
122 confirmed or probable cases of human monkeypox were recorded in 17 states, including seven deaths (case fatality rate 6%). People infected with monkeypox virus were aged between 2 days and 50 years (median 29 years [IQR 14]), and 84 (69%) were male. All 122 patients had vesiculopustular rash, and fever, pruritus, headache, and lymphadenopathy were also common. The rash affected all parts of the body, with the face being most affected. The distribution of cases and contacts suggested both primary zoonotic and secondary human-to-human transmission. Two cases of health-care-associated infection were recorded. Genomic analysis suggested multiple introductions of the virus and a single introduction along with human-to-human transmission in a prison facility.
Interpretation:
This study describes the largest documented human outbreak of the west African clade of the monkeypox virus. Our results suggest endemicity of monkeypox virus in Nigeria, with some evidence of human-to-human transmission. Further studies are necessary to explore animal reservoirs and risk factors for transmission of the virus in Nigeria.
Funding:
None.
Recently, concern has been raised about the emergence of human monkeypox virus and the occasionally severe clinical presentation bearing resemblance to that of smallpox. In 2018 3 patients in the UK were diagnosed with monkeypox, and the frequency and geographic distribution of cases across West and Central Africa have increased in recent years. In Nigeria, most monkeypox patients are aged <40 years and lack cross-protective immunity because they were born after discontinuation of the smallpox eradication campaign. This article reviews the epidemiology, clinical features, and management of monkeypox and discusses its growing public health threat in this context.
This report outlines recommendations for the clinical use of the three smallpox vaccines stored in the U.S. Strategic National Stockpile for persons who are exposed to smallpox virus or at high risk for smallpox infection during a postevent vaccination program following an intentional or accidental release of the virus. No absolute contraindications exist for smallpox vaccination in a postevent setting. However, several relative contraindications exist among persons with certain medical conditions. CDC recommendations for smallpox vaccine use were developed in consideration of the risk for smallpox infection, risk for an adverse event following vaccination, and benefit from vaccination. Smallpox vaccines are made from live vaccinia viruses that protect against smallpox disease. They do not contain variola virus, the causative agent of smallpox. The three smallpox vaccines stockpiled are ACAM2000, Aventis Pasteur Smallpox Vaccine (APSV), and Imvamune. Surveillance and containment activities including vaccination with replication-competent smallpox vaccine (i.e., vaccine viruses capable of replicating in mammalian cells such as ACAM2000 and APSV) will be the primary response strategy for achieving epidemic control. Persons exposed to smallpox virus are at high risk for developing and transmitting smallpox and should be vaccinated with a replication-competent smallpox vaccine unless severely immunodeficient. Because of a high likelihood of a poor immune response and an increased risk for adverse events, smallpox vaccination should be avoided in persons with severe immunodeficiency who are not expected to benefit from vaccine, including bone marrow transplant recipients within 4 months of transplantation, persons infected with HIV with CD4 cell counts <50 cells/mm3, and persons with severe combined immunodeficiency, complete DiGeorge syndrome, and other severely immunocompromised states requiring isolation. If antivirals are not immediately available, it is reasonable to consider the use of Imvamune in the setting of a smallpox virus exposure in persons with severe immunodeficiency. Persons without a known smallpox virus exposure might still be at high risk for developing smallpox infection depending on the magnitude of the outbreak and the effectiveness of the public health response. Such persons will be defined by public health authorities and should be screened for relative contraindications to smallpox vaccination. Relative contraindications include atopic dermatitis (eczema), HIV infection (CD4 cell counts of 50-199 cells/mm3), other immunocompromised states, and vaccine or vaccine-component allergies. Persons with relative contraindications should be vaccinated with Imvamune when available and authorized for use by the Food and Drug Administration. These recommendations will be updated as new data on smallpox vaccines become available and further clinical guidance for other medical countermeasures including antivirals is developed.
In the three decades since the eradication of smallpox and cessation of routine vaccination, the collective memory of the devastating epidemics caused by this orthopoxvirus has waned, and the human population has become increasingly susceptible to a disease that remains high on the list of possible bioterrorism agents. Research using surrogate orthopoxviruses in their natural hosts, as well as limited variola virus research in animal models, continues worldwide; however, interpretation of findings is often limited by our relative lack of knowledge about the naturally occurring disease. For modern comparative pathologists, many of whom have no first-hand knowledge of naturally occurring smallpox, this work provides a contemporary review of this historical disease, as well as discussion of how it compares with human monkeypox and the corresponding diseases in macaques.
Data on monkeypox in Zaire over the five years 1980-1984 are analysed to assess the protection imparted by past smallpox vaccination and the transmission potential of the virus in unvaccinated communities. Attack rates in individuals with and without vaccination scars indicated that smallpox vaccination (discontinued in 1980) imparted approximately 85% protection against monkeypox. It is predicted that monkeypox virus will continue to be introduced into human communities from animal sources, and that the average magnitude and duration of monkeypox epidemics will increase as vaccine-derived protection declines in the population. On the other hand, current evidence indicates that the virus is appreciably less transmissible than was smallpox, and that it will not persist in human communities, even in the total absence of vaccination. The findings thus support the recommendation of the Global Commission for the Certification of Smallpox Eradication to cease routine smallpox vaccination in monkeypox endemic areas, but to encourage continued epidemiological surveillance.
Human monkeypox is a zoonosis occurring sporadically in the tropical rain forest of western and central Africa. The exact incidence and geographical distribution are unknown, since many cases are not recognized. Special surveillance was established in three regions in Zaire in 1981 that led to a substantial increase in reported cases. The question arose as to the possibility that clinical diagnostic errors cause some cases of monkeypox to be misdiagnosed as other eruptive diseases. This paper presents the results of a study assessing the extent of and reasons for these clinical diagnostic errors in areas where health staff as well as the general public are aware of human monkeypox. In Zaire in the period 1981-1986, 977 persons with skin eruption not clinically diagnosed as human monkeypox were laboratory tested. 3.3% of human monkeypox cases were found among 730 patients diagnosed as cases of chickenpox, 7.3% among cases diagnosed as "atypical chickenpox" and 6.1% among cases with skin rash for which clinical diagnosis could not be established. The diagnostic difficulties were mainly based on clinical features characteristic of chickenpox: regional pleomorphism (in 46% of misdiagnosed cases), indefinite body-distribution of skin eruptions (49%), and centripetal distribution of skin lesions (17%). Lymph-node enlargement was observed in 76% of misdiagnosed patients. In the absence of smallpox, the main clinical diagnostic problem is the differentiation of human monkeypox from chickenpox. The presence of lymphadenopathy, pre-eruptive fever and slower maturation of skin lesions are the most important clinical signs supporting correct diagnosis of monkeypox.
We present the clinical features and course of 282 patients with human monkeypox in Zaire during 1980–1985. The ages of the
patients ranged from one month to 69 years; 90% were <15 years of age. The clinical picture was similar to that of the ordinary
and modified forms of smallpox. Lymphadenopathy, occurring in the early stage of the illness, was the most important sign
differentiating human monkeypox from smallpox and chickenpox. The symptoms, signs, and the course of the disease in patients
who had been vaccinated against smallpox differed significantly from those in unvaccinated subjects. Pleomorphism and “cropping”
similar to that in chickenpox occurred in 31% of vaccinated and 18% of unvaccinated patients. The prognosis depended largely
on the presence of severe complications. No deaths occurred among vaccinated patients. In unvaccinated patients the crude
case-fatality rate was 11 070 but was higher among the youngest children (15%).
Rapid identification and differentiation of orthopoxviruses by PCR were achieved with primers based on genome sequences encoding the hemagglutinin (HA) protein, an infected-cell membrane antigen that distinguishes orthopoxviruses from other poxvirus genera. The initial identification step used a primer pair of consensus sequences for amplifying an HA DNA fragment from the three known North American orthopoxviruses (raccoonpox, skunkpox, and volepox viruses), and a second pair for amplifying virtually the entire HA open reading frame of the Eurasian-African orthopoxviruses (variola, vaccinia, cowpox, monkeypox, camelpox, ectromelia, and gerbilpox viruses). RsaI digest electropherograms of the amplified DNAs of the former subgroup provided species differentiation, and TaqI digests differentiated the Eurasian-African orthopoxviruses, including vaccinia virus from the vaccinia virus subspecies buffalopox virus. Endonuclease HhaI digest patterns distinguished smallpox variola major viruses from alastrim variola minor viruses. For the Eurasian-African orthopoxviruses, a confirmatory step that used a set of higher-sequence-homology primers was developed to provide sensitivity to discern individual virus HA DNAs from cross-contaminated orthopoxvirus DNA samples; TaqI and HhaI digestions of the individual amplified HA DNAs confirmed virus identity. Finally, a set of primers and modified PCR conditions were developed on the basis of base sequence differences within the HA genes of the 10 species, which enabled production of a single DNA fragment of a particular size that indicated the specific species.
The history of smallpox, from its probable origin 3000 to 6000 years ago to its worldwide eradication in 1978, is a fascinating story. A feared infection, even today, smallpox has caused the deaths of millions of people and disfigured many. This article describes the possible origin of the infection and traces its progress throughout the world. The introduction of inoculation with material from smallpox lesions and vaccination using cowpox virus is described. The World Health Organization's successful smallpox eradication program in the 1960s and 1970s is described. Personal experience of this program in Bangladesh in 1973 is outlined, as is the laboratory escape of the major smallpox virus in Birmingham in 1978. The possible use of the smallpox virus as a biological weapon is discussed.