Assuming all individuals behaved similarly, this is unlikely to have materially affected the serial interval distribution. The UK has seen 82 new monkeypox cases this week and a total of 190 cases so far. 10 out of 13 linked patients had documented pre-symptomatic transmission. In the analysis, we assume that the direction of transmission is based on the date order of symptom onset, because the direction of transmission cannot be otherwise ascertained. CDC has also warned clinicians to not rule out monkeypox in patients with sexually transmitted infections since there have been reports of co-infections with syphilis, gonorrhea, chlamydia, and herpes.[26]. Monkeypox was first detected in 1970 in the Democratic Republic of the Congo, The incubation period and serial interval have been estimated from observational studies, Since the international outbreak of monkeypox in May 2022 a study estimated a mean incubation period of 8.5 days; however, the sample size was small (n=18), This study found evidence of pre-symptomatic transmission of monkeypox, using contact tracing data and adjustments for interval censoring, right truncation, and epidemic phase bias, The maximum time that transmission was detected before symptoms manifested for infected individuals who could be linked through reliable personal identifiable information was four days. 4. UK Health Security Agency. The Food and Drug Administration (FDA) is urging that providers be "judicious" in prescribing the The MCMC algorithm preferentially selects parameters that better describe the data. Britain should be stockpiling . A Weibull distribution gave the best fit to the data for both models (see supplementary material A for results of the lognormal and gamma models). Further details on the epidemiology are available in the monkeypox technical briefing. TW, CO, RP, and RC developed the model code and wrote the original manuscript. For the more reliable sample where personal identifiable information was available for linkage, this time decreased to four days, with three out of the four more reliable (ie, personal identifiable information available) case-contact pairs showing pre-symptomatic transmission. 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. [33], On 30 August 2022, 3413 cumulative cases (3,279 confirmed and 134 highly probable cases) of human monkeypox up to (and including) 29 August were reported for the UK. Copyright 2023 BMJ Publishing Group Ltd, A systematic review of the epidemiology of human monkeypox outbreaks and implications for outbreak strategy, Comparison of West African and Congo Basin monkeypox viruses in BALB/c and C57BL/6 mice, Virulence differences between monkeypox virus isolates from West Africa and the Congo basin, On the relationship between serial interval, infectiousness profile and generation time, Presymptomatic transmission of SARS-CoV-2 infection: a secondary analysis using published data, Serial interval of novel coronavirus (COVID-19) infections, Human monkeypox: disease pattern, incidence and attack rates in a rural area of northern Zaire, Extended Human-to-Human Transmission during a Monkeypox Outbreak in the Democratic Republic of the Congo, Estimated incubation period for monkeypox cases confirmed in the Netherlands, May 2022, Understanding an evolving pandemic: An analysis of the clinical time delay distributions of COVID-19 in the United Kingdom, Hospital length of stay for COVID-19 patients: Data-driven methods for forward planning, Inference from Iterative Simulation Using Multiple Sequences, Estimating a time-to-event distribution from right-truncated data in an epidemic: A review of methods, Growth, reproduction numbers and factors affecting the spread of SARS-CoV-2 novel variants of concern in the UK from October 2020 to July 2021: a modelling analysis, Estimating incubation period distributions with coarse data, Shorter incubation period is associated with severe disease progression in patients with COVID-19, Brief Report: Incubation Period Duration and Severity of Clinical Disease Following Severe Acute Respiratory Syndrome Coronavirus Infection, Association between Severity of MERS-CoV Infection and Incubation Period, Incubation period, severity of disease, and infecting dose: evidence from a Salmonella outbreak, Surveillance, case investigation and contact tracing for monkeypox: interim guidance, 25 August 2022, Transmission dynamics of monkeypox in the United Kingdom: contact tracing study, https://www.gov.uk/government/publications/accessing-ukhsa-protected-data/accessing-ukhsa-protected-data, https://github.com/OvertonC/Transmission-Dynamics-of-Monkeypox-in-the-United-Kingdom, http://creativecommons.org/licenses/by-nc/4.0/, https://www.who.int/news-room/fact-sheets/detail/monkeypox, https://www.who.int/emergencies/disease-outbreak-news/item/2022-DON385, https://www.gov.uk/government/publications/monkeypox-outbreak-epidemiological-overview/monkeypox-outbreak-epidemiological-overview-13-september-2022, https://www.who.int/europe/news/item/23-07-2022-who-director-general-declares-the-ongoing-monkeypox-outbreak-a-public-health-event-of-international-concern, https://www.gov.uk/government/publications/principles-for-monkeypox-control-in-the-uk-4-nations-consensus-statement/principles-for-monkeypox-control-in-the-uk-4-nations-consensus-statement#:~:text=In%20the%20UK%2C%20all%20reported,about%20the%20West%20Afr, https://mc-stan.org/rstanarm/reference/loo.stanreg.html, https://www.ecdc.europa.eu/sites/default/files/documents/Considerations-for-Contact-Tracing-MPX_June%202022.pdf, https://www.gov.uk/government/publications/monkeypox-outbreak-technical-briefings/investigation-into-monkeypox-outbreak-in-england-technical-briefing-1#part-2-epidemiology-update, https://www.gov.uk/government/publications/monkeypox-outbreak-technical-briefings/investigation-into-monkeypox-outbreak-in-england-technical-briefing-3, https://web.archive.org/web/20220605103903/https://www.who.int/emergencies/disease-outbreak-news/item/monkeypox-democratic-republic-of-the-congo, https://www.gov.uk/government/publications/monkeypox-outbreak-technical-briefings/investigation-into-monkeypox-outbreak-in-england-technical-briefing-1#part-3-genomics, https://www.who.int/publications/i/item/WHO-MPX-Surveillance-2022.3, Birmingham and Solihull Mental Health NHS Foundation Trust: Consultant Psychiatrist General Adult - Northcroft CMHT, Brent Area Medical Centre: Salaried GP - Brent Area Medical Centre, Onebright Ltd: Consultant Psychiatrist (Neurodiversity) - Remote / London, The Royal Hospital for Neurodisability: Clinical Fellow, Womens, childrens & adolescents health. [5][7] The classic presentation of fever and muscle pains, followed by swollen glands, with lesions all at the same stage, has not been found to be common to all outbreaks. Mpox (also known as monkeypox) is an infectious viral disease that can occur in humans and some other animals. The shorter median estimate for the serial interval relative to the incubation period suggests that pre-symptomatic transmission might be more substantial than was previously thought, which is further supported by linked patient level data. 2020 Election Business Tech . We did not directly involve patients and members of the public in the design and conception of the study, primarily because of the pace at which this study was conducted to inform the UK governments response to the monkeypox outbreak in the UK. With the emergence of COVID-19 and the recent surge in monkeypox cases, scientists and doctors who specialize in infectious disease are issuing increasingly dire warnings, saying wealthy countries can no longer afford to ignore small outbreaks abroad. With more than 16,800 cases globally, some scientists are calling the monkeypox outbreak a pandemic, albeit with a far lower mortality rate than the COVID-19 pandemic. UK Health Security Agency. The DRC reported more than 18,000 confirmed or suspected monkeypox cases from 2010 to 2019, up from about 10,000 from 2000 to 2009, and more than 6,000 suspected cases in 2020. This relies on the assumption that the primary case identified by the secondary contact in the questionnaire is the same primary case identified in case-contact pair. As the global monkeypox outbreak lingers on, health officials are warning that the virus is mutating at a pace that may soon allow it to become resistant to an antiviral drug used to treat patients at risk of serious illness. Setting Case questionnaires from the UK Health Security Agency (UKHSA), United Kingdom. There's a monkeypox outbreak in the United Kingdom, Portugal, Spain and other European countries. Cases of monkeypox infection were confirmed in England from 6 May 2022. Design Contact tracing study, linking data on case-contact pairs and on probable exposure dates. How you get monkeypox Monkeypox can be passed on from person to person through: To help us improve GOV.UK, wed like to know more about your visit today. These priors were chosen to be sufficiently informative to penalise unrealistic parameter combinations but specified with low precision to allow the data to maximally inform the estimates. England counts may differ from those published in the Notifications of infectious diseases (NOIDs) causative agents weekly report. However, this would be computationally expensive. If an epidemic is stable or declining the right truncation bias has less of an effect on the data. Dont worry we wont send you spam or share your email address with anyone. Greater uncertainty can be observed for the model that adjusts for right truncation. Since early May 2022, cases of mpox (monkeypox) have been reported from countries where the disease is not endemic, and continue to be reported in several endemic countries. The data sharing section includes a link to a repository containing the code for the model and the trace results from the MCMC sample. This question is for testing whether or not you are a human visitor and to prevent automated spam submissions. 2020. When negative incubation periods were identified, we assumed that the patient was not infected by the named contact, as this is not possible. There may be mild symptoms, and it may occur . This is due to differences in timings of when the data is compiled, and differences in processing of duplicate data (for example, if a person has tested more than once but insufficient information is provided to identify them). Such spread has resulted in divergence of the virus, with two distinct clades circulating in different regions of Africa. However, anyone, regardless of sexual orientation or gender identity, who has been in close, personal contact with someone who has mpox is at risk. The first known case was detected in the beginning of May 2022, in a British resident who had travelled to Lagos and Delta State in Nigeria,[27] in areas where monkeypox is considered to be an endemic disease. These estimates are specific to the demographic distribution of this outbreak (age and sexual orientation) and severity of this clade. Investigation into monkeypox outbreak in England: technical briefing 3. [2], Mpox (also known as monkeypox[3]) is an infectious viral disease that can occur in humans and some other animals. The World Health Organization said Tuesday that a recent outbreak of monkeypox cases in non-endemic countries is "containable," even as it continues to confound health experts. The first case was reported in Vienna, Austria, on May 22, 2022. WHO. A high proportion of England cases were London residents (69%, 2,397 of 3,467 with location information). For instance, even though monkeypox can be prevented, detected, and treated with the use of vaccines, medicines, and diagnostics, further studies are required to help establish the appropriate use of these . Firstly, we linked case-contact pairs to questionnaire records for each secondary contact, which enabled the primary case and the exposure date to be identified for the secondary contact. The growing number prompted the World Health Organization (WHO) to declare monkeypox a global health emergency, as it did for COVID-19 in 2020. Update on Monkeypox in Children, Adolescents, and People Who are Pregnant or Breastfeeding; Melioidosis in the United States: What Clinicians Need to Know Following Newly Discovered Endemicity; Update on 2022 Ebola Outbreak in Uganda; Situational Update for Clinicians about Severe Monkeypox Virus Infections Nigeria has. Objective To analyse the transmission dynamics of the monkeypox outbreak in the UK, declared a Public Health Emergency of International Concern in July 2022. Taha, M. J., Abuawwad, M. T., Alrubasy, W. A., Sameer, S. K., Alsafi, T., Al-Bustanji, Y., & Nashwan, A. J. Ocular manifestations of recent viral pandemics: A literature. *Personal identifiable information not available and therefore data considered less reliable. Data were extracted as of 1 August 2022, at which time 2746 people had been identified with monkeypox in the UK. Investigation into monkeypox outbreak in England: technical briefing 1. It will take only 2 minutes to fill in. The CDC has also stated that individuals should avoid contact and consumption of dead animals such as rats, squirrels, monkeys and apes along with wild game or lotions derived from animals in Africa. Funding: The authors were employed by the UK Health Security Agency but received no specific funding for this study. However, since serial intervals depend on the incubation period this finding is an approximation of the proportion of infections due to pre-symptomatic transmission. This update is currently published on Tuesdays, using data extracted by 9.30am on Mondays. United States now has the world's biggest outbreak of monkeypox: . Short serial intervals were more common than short incubation periods suggesting considerable pre-symptomatic transmission, which was validated through linked patient level records. Monkeypox is a zoonotic infection, caused by the monkeypox virus, that occurs mostly in West and Central Africa. The 95th centile of the serial interval was between 23 and 41 days, suggesting long infectious periods. The outbreak could spread beyond U.K. borders, the agency said, particularly because there appears . Work was undertaken in line with national data regulations. [4] The time from exposure to onset of symptoms ranges from five to twenty-one days. Data are obtained from three types of questionnaires: A questionnaire administered by health practitioners, An anonymous self-completed questionnaire, All questionnaires are optional, and individuals are not required to complete all questions. Posterior distributions for mean and standard deviation of the serial interval for monkeypox. This study was conducted for the purpose of informing the outbreak response to the monkeypox pandemic. To compare the model fits we calculated the leave-one-out cross validation (LOO) through Pareto smoothed importance sampling, using the LOO package in R.19 We applied MCMC to each model and evaluated its convergence using potential scale reduction factor, or (calculated using Cmdstanr20), where it is desirable to have a value <1.05. All requests to access data are reviewed by the Office for Data Release and are subject to strict confidentiality provisions in line with the requirements of: the common law duty of confidentiality, data protection legislation (including the General Data Protection Regulation), Caldicott principles, the Information Commissioners statutory data sharing code of practice, and the national data opt-out programme. [4] Symptoms include fever, swollen lymph nodes, and a rash that forms blisters and then crusts over. Counts of confirmed cases in Wales, Northern Ireland, and Scotland are submitted to UKHSA by Public Health Wales, Public Health Agency Northern Ireland, and Public Health Scotland respectively. [29], On 30 May, the four main public health agencies published a consensus statement describing the principles they will put in use, with the aim of limiting community transmission. To estimate the exponential growth rate, we need to assume an exponential structure to the data. To adjust for the right truncation, we fitted a double interval censoring and right truncation corrected parametric delay distribution. Updates on EU/EEA countries, the Western Balkans and Trkiye An isolation period of 16 to 23 days would be required to detect 95% of people with a potential infection. Many countries around the world, including the UK, have started using smallpox vaccines to prevent smallpox as the two viruses are similar. The outbreak has mainly been in gay, bisexual, and men who have sex with men without documented history of travel to endemic countries. Monkeypox is a misnomer that results from the fact that it was discovered at the Statens Serum Institut in Copenhagen in 1958, when outbreaks of a pox-like disease occurred in monkeys kept for. This finding is consistent with the proportion of pre-symptomatic transmission among the subset of case-contact pairs where transmission can be identified relative to the date of symptom onset after exposure. Figure 5 shows the relative times from the symptom onset date in the primary case (primary case onset) to the date of exposure for the secondary contact (secondary contact exposure), serial interval, and the incubation period of the 13 case-contact pairs for whom all events could be linked. By the most recent modelled dates (15 September) case numbers were declining relatively quickly and halving every 16.89 days (27.40 to 12.19). [22] The origin of several of the cases of mpox in the United Kingdom is unknown. Infection control precautions for contacts (vaccination, daily monitoring, staying home from work) were implemented. Data for both the serial interval and the incubation period are similarly distributed across the monkeypox outbreak in the UK, so temporal changes in reporting should affect both distributions comparably (see supplementary material C). Analysis of these 13 case-contact pairs showed 10 with pre-symptomatic transmission. Doubling times of cases declined from 9.07 days (95% confidence interval 12.63 to 7.08) on the 6 May, when the first case of monkeypox was reported in the UK, to a halving time of 29 days (95% confidence interval 38.02 to 23.44) on 1 August. Incubation periods and serial intervals are examples of time delay distributions, which describe the distribution of times between two coupled events. You have accepted additional cookies. UK Health Security Agency. ECDC. We have assumed that transmission follows the direction of symptom onset dates. Data requests can be made to the Office for Data Release (https://www.gov.uk/government/publications/accessing-ukhsa-protected-data/accessing-ukhsa-protected-data) and by contacting DataAccess@ukhsa.gov.uk. A total of 220 case-contact pairs were reported in HPZone, 79 with a symptom onset date for both individuals in the case-contact pair, forming our serial interval cohort. The World Health Organization has said another 50 suspected cases are being investigated - without naming any. Main outcome measures The incubation period and serial interval of a monkeypox infection using two bayesian time delay modelsone corrected for interval censoring (ICCinterval censoring corrected) and one corrected for interval censoring, right truncation, and epidemic phase bias (ICRTCinterval censoring right truncation corrected). Named contacts are therefore likely to correspond to genuine transmission events. Later cases had no link to the first case, and those infected hadn't traveled to where monkeypox is endemic. May 19, 2022. These figures are used for official reporting of monkeypox confirmed case counts in the UK. Well send you a link to a feedback form. An application can be made to the UK Health Security Agency. TW, CO, and FC reviewed the manuscript. We used a previously described method22 to estimate the growth rate of monkeypox cases since the start of the outbreak in England. This gives greater confidence in the conclusions because they are not driven by methodological choices. Right truncation emerges when data are only observed after the second event occurs, such as infections being identified only after cases emerge. For the ICC and ICRTC models, the corresponding estimates ranged from 1.8 days (95% credible interval 1.5 to 1.8) to 1.6 days (1.4 to 1.6) shorter at the 25th centile and 1.6 days (1.5 to 1.7) to 0.8 days (0.3 to 1.2) shorter at the median. For the serial interval, this is the time between the symptom onset date in the primary case (primary event) and the symptom onset date in the secondary contact (secondary event). 2022. A milder West African strain of the virus is driving the. These 13 form our cohort for investigating pre-symptomatic transmission. Red arrow indicates number of days between primary onset and secondary onset (serial interval). To obtain the serial interval data we used self-reported symptom onset dates and linked case-contact pairs (linked pairs of primary and secondary cases). The two clades, the Congo Basin and Western African, show distinct epidemiological characteristics. Between 6 May 2022 and 12 September 2022, 3552 cases of monkeypox have been confirmed in the United Kingdom.7 The international dispersion of the virus has resulted in the largest outbreak of monkeypox reported outside of Africa. The right truncation primarily affects recent observations and has less of an influence on older observations. Monkeypox - Democratic Republic of the Congo. Analysis of the instantaneous growth rate indicates that as of 9 July the epidemic peaked in the UK. We use some essential cookies to make this website work. During May 17-September 24, 2022, a total of 25,038 monkeypox cases were reported in the United States . Although the outbreak was large, however, incidence was still low relative to the population size at risk. The outbreak is small so far about 80 suspected cases in England, Spain and Canada as well. Of these, 94 were in Scotland, 34 were in Northern Ireland, 46 were in Wales and 3,480 were in England. Ufulu on Monkeypox outbreak can still be contained, insists UN health agency. the next day, This page was last edited on 28 February 2023, at 10:29. [29][30] Public Health Wales and the Public Health Agency of Northern Ireland each reported one case on 26 May. In this method, we assume that the primary event (symptom onset in the primary case for serial interval or exposure date for incubation period) for each individual sits within an interval [e1, e2], where e1 is the reported event date and e2 is the day after. Other approaches can be applied to handle right truncation bias.21 We opted for our approach because the epidemic phase related terms, P(E=e*), cancel each other out, so we do not need to explicitly describe the phase of the epidemic within the model. Confirmed cases include those laboratory-confirmed as mpox virus and may include cases only confirmed as orthopoxvirus. However, this overestimation of the serial interval will bias the data away from pre-symptomatic transmission, which further supports the evidence of pre-symptomatic transmission we identified. We defined a confirmed case as an individual with a positive polymerase chain reaction (PCR) test result for monkeypox virus, and a highly probable case as an individual with a positive PCR test result for orthopoxvirus. To estimate this smooth function, we fit a generalised additive model to daily confirmed case counts with a negative binomial error structure and log link. Cases had the option of answering On what date did your illness begin?, In the 21 days (3 weeks) before first symptom onset did you have contact with anyone with suspected or confirmed monkeypox infection?, and Date of last contact with case. An exposure date was therefore defined as the last date an individual reported contact with a known case in the 21 days before symptoms manifested, and symptom onset was defined as the date symptoms manifested. From early May 2022 to September 21, 2022, 61,753 confirmed . Figure 6 shows the instantaneous growth rate of case numbers over time and log scale model fit to case counts. 2. TW and CO developed the methodology. On 6 May 2022, monkeypox was detected in England in a patient who had recently travelled to Nigeria. To investigate potential exposure dates that occurred before symptom onset in a primary case, which would suggest pre-symptomatic transmission, we linked data on the date of symptom onset in the primary case with exposure dates in their secondary contacts. In 2020, less than 10% of the largest global health organizations were head-quartered in the African region, and very few of the global health organizations are led by African nationals . Recently, sporadic MPXV infections in several nonendemic countries have attracted widespread attention. We identified exposure dates for the incubation period from questionnaire data filled out by cases. The Atlantic. Although case numbers are declining, increased international transmission would facilitate infection importation and might drive stochastic outbreaks even if vaccination in local networks limits transmission. As of July 26, 3,591 cases in 46 states, Puerto Rico, and Washington, D.C., have been diagnosed (see . In such cases it may be reasonable to consider a model without the right truncation correctionthat is, assuming that P(S