Post by Nadica (She/Her) on Aug 23, 2024 0:07:35 GMT
Transmission dynamics of monkeypox in the United Kingdom: contact tracing study - Published Nov 2, 2022
Abstract
Objective To analyse the transmission dynamics of the monkeypox outbreak in the UK, declared a Public Health Emergency of International Concern in July 2022.
Design Contact tracing study, linking data on case-contact pairs and on probable exposure dates.
Setting Case questionnaires from the UK Health Security Agency (UKHSA), United Kingdom.
Participants 2746 people with polymerase chain reaction confirmed monkeypox virus in the UK between 6 May and 1 August 2022.
Main outcome measures The incubation period and serial interval of a monkeypox infection using two bayesian time delay models—one corrected for interval censoring (ICC—interval censoring corrected) and one corrected for interval censoring, right truncation, and epidemic phase bias (ICRTC—interval censoring right truncation corrected). Growth rates of cases by reporting date, when monkeypox virus was confirmed and reported to UKHSA, were estimated using generalised additive models.
Results The mean age of participants was 37.8 years and 95% reported being gay, bisexual, and other men who have sex with men (1160 out of 1213 reporting). The mean incubation period was estimated to be 7.6 days (95% credible interval 6.5 to 9.9) using the ICC model and 7.8 days (6.6 to 9.2) using the ICRTC model. The estimated mean serial interval was 8.0 days (95% credible interval 6.5 to 9.8) using the ICC model and 9.5 days (7.4 to 12.3) using the ICRTC model. Although the mean serial interval was longer than the incubation period for both models, short serial intervals were more common than short incubation periods, with the 25th centile and the median of the serial interval shorter than the incubation period. 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. 10 out of 13 linked patients had documented 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.
Conclusions Analysis of the instantaneous growth rate of monkeypox incidence indicates that the epidemic peaked in the UK as of 9 July and then started to decline. Short serial intervals were more common than short incubation periods suggesting considerable pre-symptomatic transmission, which was validated through linked patient level records. For patients who could be linked through personally identifiable data, four days was the maximum time that transmission was detected before symptoms manifested. An isolation period of 16 to 23 days would be required to detect 95% of people with a potential infection. The 95th centile of the serial interval was between 23 and 41 days, suggesting long infectious periods.
ATTACHED EDITORIAL: The dynamics of monkeypox transmission - Published Nov 2, 2022
Pre-exposure vaccination and vaccine equity are urgently needed worldwide
After a surge of monkeypox infections starting in May 2022, with more than 70 000 cases globally—including 99% from countries without previous known endemic spread—by the end of August 2022, new infections started to trend downward.12 Whether this marks the end of the outbreak or whether intermittent surges will continue is not yet clear. Understanding the underlying transmission dynamics is key to shedding light on this, as well as informing future interventions.
In a linked paper, Ward and colleagues (doi:10.1136/bmj-2022-073153) used routine case questionnaires and contact tracing data to estimate two important characteristics of the monkeypox outbreak in the UK: the serial interval and incubation period.3 They found that shorter serial intervals are more common than shorter incubation periods. One explanation the authors provided is that considerable transmission is occurring before the appearance or detection of symptoms; otherwise, the serial interval should at a minimum equal the incubation period.
This study had a relatively large sample size and appropriate statistical adjustments to account for key biases in the data. The researchers used paired case-contact data to validate their model based conclusions. One limitation was the use of patient reported variables, with the potential for recall and response biases, which is particularly critical for the date of symptom onset. For example, people who have been contact traced or reached by public health messages will be more aware of potential symptoms and therefore likely more vigilant. If infected individuals notice symptoms sooner than those who infected them, the serial interval, and therefore the comparison with the incubation period, could be biased. Contact tracing, with individuals self-reporting exposure events, is used to link people who infect others and those who become infected and could also be a source of bias. For example, in the case of monkeypox infection after a superspreading event where the index case was not identified, the serial interval could be underestimated.4
Other studies have also hinted at pre-symptomatic transmission. Anal swabs collected from 213 asymptomatic men who have sex with other men were retrospectively screened for monkeypox virus; 13 tested positive on polymerase chain reaction (PCR) and two subsequently developed symptoms.5 Although a positive PCR test result does not necessarily indicate that an individual is infectious, this study raised questions about transmission being dependent on symptoms.
Evidence supporting pre-symptomatic transmission is not definitive, but if Ward and colleagues’ findings are supported by those of other studies, then pre-symptomatic transmission, or transmission before symptoms are detected, would have important implications for infection control globally. Specifically, postexposure or “ring” vaccination of contacts identified only through individuals with symptoms, could be inadequate.56 In the US and UK, vaccination campaigns have already shifted from exclusively postexposure prophylaxis to include pre-exposure prophylaxis for some high risk groups.78
Vaccine equity
Equitable access to vaccines is critical to monkeypox control efforts globally, and lack of access is a serious concern, particularly if pre-symptomatic transmission is occurring. Currently, Jynneos (also known as Imvanex), which is in limited supply, is the primary vaccine in use for monkeypox in the US, Canada, Europe, and the UK910; the older smallpox vaccine ACAM2000 is less commonly used and only in select patients.11
From the patient perspective, monkeypox infection can be extremely painful and isolating, greatly affecting psychological wellbeing.1213 High risk communities are keen to access vaccination, as evidenced by long vaccination queues.1415 Ensuring that effective vaccines are available to all communities and individuals at risk should be a priority for health leaders in affected countries, and for global health leaders more broadly.
In the US, for example, black people account for 50% of monkeypox infections but received only 12% of the vaccines.1617 In Nigeria, where monkeypox is endemic, vaccines are currently unavailable so no vaccination policy of any kind can be implemented, an inequity reminiscent of the covid-19 pandemic.1819 This is also the case for many other African countries.
From a health system perspective, vaccination is likely to be more cost effective than managing the consequences of preventable infections, including hospital admissions, loss of income during isolation, and long term complications. These costs put extra pressure on health systems in low income countries that already have a high burden of infectious diseases.
Public health measures that have been critical during monkeypox outbreaks in high income countries, such as PCR testing and vaccination, remain unavailable in much of Africa.9 In their study, Ward and colleagues from the UK Health Security Agency relied on resource intensive contact tracing and case questionnaires—approaches important to a context specific public health response but under-supported in low resource countries where monkeypox is endemic.
As the monkeypox outbreak declines in Europe and North America, we have a responsibility to deploy effective tools for viral control on a global level—not just in wealthy nations. These tools include research into understanding transmission dynamics in African settings and the inclusion of endemic countries in vaccine trials.
Abstract
Objective To analyse the transmission dynamics of the monkeypox outbreak in the UK, declared a Public Health Emergency of International Concern in July 2022.
Design Contact tracing study, linking data on case-contact pairs and on probable exposure dates.
Setting Case questionnaires from the UK Health Security Agency (UKHSA), United Kingdom.
Participants 2746 people with polymerase chain reaction confirmed monkeypox virus in the UK between 6 May and 1 August 2022.
Main outcome measures The incubation period and serial interval of a monkeypox infection using two bayesian time delay models—one corrected for interval censoring (ICC—interval censoring corrected) and one corrected for interval censoring, right truncation, and epidemic phase bias (ICRTC—interval censoring right truncation corrected). Growth rates of cases by reporting date, when monkeypox virus was confirmed and reported to UKHSA, were estimated using generalised additive models.
Results The mean age of participants was 37.8 years and 95% reported being gay, bisexual, and other men who have sex with men (1160 out of 1213 reporting). The mean incubation period was estimated to be 7.6 days (95% credible interval 6.5 to 9.9) using the ICC model and 7.8 days (6.6 to 9.2) using the ICRTC model. The estimated mean serial interval was 8.0 days (95% credible interval 6.5 to 9.8) using the ICC model and 9.5 days (7.4 to 12.3) using the ICRTC model. Although the mean serial interval was longer than the incubation period for both models, short serial intervals were more common than short incubation periods, with the 25th centile and the median of the serial interval shorter than the incubation period. 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. 10 out of 13 linked patients had documented 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.
Conclusions Analysis of the instantaneous growth rate of monkeypox incidence indicates that the epidemic peaked in the UK as of 9 July and then started to decline. Short serial intervals were more common than short incubation periods suggesting considerable pre-symptomatic transmission, which was validated through linked patient level records. For patients who could be linked through personally identifiable data, four days was the maximum time that transmission was detected before symptoms manifested. An isolation period of 16 to 23 days would be required to detect 95% of people with a potential infection. The 95th centile of the serial interval was between 23 and 41 days, suggesting long infectious periods.
ATTACHED EDITORIAL: The dynamics of monkeypox transmission - Published Nov 2, 2022
Pre-exposure vaccination and vaccine equity are urgently needed worldwide
After a surge of monkeypox infections starting in May 2022, with more than 70 000 cases globally—including 99% from countries without previous known endemic spread—by the end of August 2022, new infections started to trend downward.12 Whether this marks the end of the outbreak or whether intermittent surges will continue is not yet clear. Understanding the underlying transmission dynamics is key to shedding light on this, as well as informing future interventions.
In a linked paper, Ward and colleagues (doi:10.1136/bmj-2022-073153) used routine case questionnaires and contact tracing data to estimate two important characteristics of the monkeypox outbreak in the UK: the serial interval and incubation period.3 They found that shorter serial intervals are more common than shorter incubation periods. One explanation the authors provided is that considerable transmission is occurring before the appearance or detection of symptoms; otherwise, the serial interval should at a minimum equal the incubation period.
This study had a relatively large sample size and appropriate statistical adjustments to account for key biases in the data. The researchers used paired case-contact data to validate their model based conclusions. One limitation was the use of patient reported variables, with the potential for recall and response biases, which is particularly critical for the date of symptom onset. For example, people who have been contact traced or reached by public health messages will be more aware of potential symptoms and therefore likely more vigilant. If infected individuals notice symptoms sooner than those who infected them, the serial interval, and therefore the comparison with the incubation period, could be biased. Contact tracing, with individuals self-reporting exposure events, is used to link people who infect others and those who become infected and could also be a source of bias. For example, in the case of monkeypox infection after a superspreading event where the index case was not identified, the serial interval could be underestimated.4
Other studies have also hinted at pre-symptomatic transmission. Anal swabs collected from 213 asymptomatic men who have sex with other men were retrospectively screened for monkeypox virus; 13 tested positive on polymerase chain reaction (PCR) and two subsequently developed symptoms.5 Although a positive PCR test result does not necessarily indicate that an individual is infectious, this study raised questions about transmission being dependent on symptoms.
Evidence supporting pre-symptomatic transmission is not definitive, but if Ward and colleagues’ findings are supported by those of other studies, then pre-symptomatic transmission, or transmission before symptoms are detected, would have important implications for infection control globally. Specifically, postexposure or “ring” vaccination of contacts identified only through individuals with symptoms, could be inadequate.56 In the US and UK, vaccination campaigns have already shifted from exclusively postexposure prophylaxis to include pre-exposure prophylaxis for some high risk groups.78
Vaccine equity
Equitable access to vaccines is critical to monkeypox control efforts globally, and lack of access is a serious concern, particularly if pre-symptomatic transmission is occurring. Currently, Jynneos (also known as Imvanex), which is in limited supply, is the primary vaccine in use for monkeypox in the US, Canada, Europe, and the UK910; the older smallpox vaccine ACAM2000 is less commonly used and only in select patients.11
From the patient perspective, monkeypox infection can be extremely painful and isolating, greatly affecting psychological wellbeing.1213 High risk communities are keen to access vaccination, as evidenced by long vaccination queues.1415 Ensuring that effective vaccines are available to all communities and individuals at risk should be a priority for health leaders in affected countries, and for global health leaders more broadly.
In the US, for example, black people account for 50% of monkeypox infections but received only 12% of the vaccines.1617 In Nigeria, where monkeypox is endemic, vaccines are currently unavailable so no vaccination policy of any kind can be implemented, an inequity reminiscent of the covid-19 pandemic.1819 This is also the case for many other African countries.
From a health system perspective, vaccination is likely to be more cost effective than managing the consequences of preventable infections, including hospital admissions, loss of income during isolation, and long term complications. These costs put extra pressure on health systems in low income countries that already have a high burden of infectious diseases.
Public health measures that have been critical during monkeypox outbreaks in high income countries, such as PCR testing and vaccination, remain unavailable in much of Africa.9 In their study, Ward and colleagues from the UK Health Security Agency relied on resource intensive contact tracing and case questionnaires—approaches important to a context specific public health response but under-supported in low resource countries where monkeypox is endemic.
As the monkeypox outbreak declines in Europe and North America, we have a responsibility to deploy effective tools for viral control on a global level—not just in wealthy nations. These tools include research into understanding transmission dynamics in African settings and the inclusion of endemic countries in vaccine trials.