DRC had hoped to receive a first round of vaccine deliveries this week as virus spreads.
The Democratic Republic of the Congo (DRC) says it no longer expects to receive its first delivery of mpox vaccines this week as global health authorities say the spread of the disease can still be contained.
Asked whether the DRC would begin receiving the doses this week, Cris Kacita, the head of the countrys response team, told the Reuters news agency on Monday: No. There are still several processes to follow.
He said the Congolese pharmaceutical regulatory agency would first need to be in touch with Danish drugmaker Bavarian Nordic for guidance before the vaccines arrive.
So were waiting, Kacita said.
The World Health Organization (WHO) said in a statement on Monday that the virus can still be prevented from spreading further but doing so requires a coordinated response.
The mpox outbreaks in the Democratic Republic of the Congo and neighboring countries can be controlled, and can be stopped, WHO Director-General Tedros Adhanom Ghebreyesus said in a statement.
The announcement came as health authorities struggle to roll back the virus, which the WHO this month declared a global public health emergency for the second time in as many years. While the vast majority of cases are concentrated in the DRC, other nations in Asia and Europe have reported cases.
On August 19, the DRC health minister had expressed optimism that the country could start receiving vaccine deliveries as early as this week after promises of assistance from Japan and the United States.
German government spokesperson Steffen Hebestreit said on Monday that the country would donate 100,000 vaccine doses as the DRC reported more than 1,000 new mpox cases last week.
The Africa Centres for Disease Control and Prevention reported that, as of Thursday, more than 21,300 suspected or confirmed cases and 590 deaths have been reported this year across 12 African nations.
The WHO said it was significantly increasing its staffing in impacted countries, part of a six-month plan announced on Monday with the aim of ensuring greater access to vaccines and improving prevention and response.
Strategic vaccination efforts will focus on individuals at the highest risk, including close contacts of recent cases and healthcare workers, to interrupt transmission chains, the agency said in a news release.
The WHO said the plan will require $135m in funding and a funding appeal will be launched shortly.
"It's a huge challenge," said Pierre-Olivier Ngadjole, a doctor with the Swiss humanitarian organization Medair, which runs the Munigi treatment center.
At the hospital in South Kivu, Nathalie's mother, Ms. Binja, said she was aware that she could be infected with mpox because of the close contact with her daughter.
But she said, I dont want to leave her alone, I dont want her to die.
Implementation of a novel scoring tool for urine culturing was associated with a more than 30% reduction in urinary antibiotic prescribing at a rehabilitation facility for long-term care (LTC) patients in Canada, researchers reported today in Infection Control & Hospital Epidemiology.
The aptly named BLADDER score was developed by clinicians at a 134-bed complex-continuing-care and rehabilitation facility in Ontario to promote more appropriate urine culturing in non-catheterized patients with presumed urinary tract infections (UTIs). Each of the letters in the score represents a possible symptom representative of UTI (B, blood in urine; L, loss of urinary control or incontinence; A, abdominal or flank pain; D, dysuria or pain on urination; E, elevated temperature or fever; R, repeated urination or frequency), with 1 point given for each letter in the algorithm; a score below 2 suggests careful monitoring of patient symptoms rather than a urine culture.
To evaluate the impact of the scoring tool, researchers compared urine culturing, urinary antibiotic use and length of stay (LOS), acute-care transfers, and mortality 18 months before and 16 months after the intervention.
Before the intervention, the mean rate of urine culturing was 12.47 cultures per 1,000 patient-days; after the intervention, the rate was 7.92 cultures per 1,000 patient-days (incidence rate ratio (IRR), 0.87; 95% confidence interval [CI], 0.67 to 1.12). Although the decline in urine culturing was not considered statistically significant, urinary antibiotic use declined significantly after the intervention, from a mean of 40.55 defined daily doses (DDD) per 1,000 patient-days before to 25.96 DDD per 1,000 patient-days after the intervention (IRR, 0.68; 95% CI, 0.59 to 0.79). There was no change in mean patient LOS, acute-care transfers, or mortality.
"The implementation of a scoring tool may be a useful adjunct to further explore in addition to other diagnostic stewardship strategies in hospitalized and LTC patients," the study authors wrote. "Such a tool may be particularly useful as part of electronic health records as a trigger to consider more judicious culturing practices."
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GENEVA -- The U.N. health agency on Monday launched a six-month plan to help stanch outbreaks of mpox transmission, including ramping up staffing in affected countries and boosting surveillance, prevention and response strategies.
The World Health Organization said it expects the plan from September through February next year will require $135 million in funding and aims to improve fair access to vaccines, notably in African countries hardest hit by the outbreak.
The mpox outbreaks in the Democratic Republic of the Congo and neighboring countries can be controlled, and can be stopped, said WHO Director-General Tedros Adhanom Ghebreyesus in a statement.
The agency is significantly scaling up staff in affected countries, it said. In mid-August, WHO classified the current mpox outbreak as a global health emergency.
Also Monday, German government spokesperson Steffen Hebestreit said Germany is donating 100,000 doses of mpox vaccine to affected countries from stocks held by its military, German news agency dpa reported.
Last Tuesday, Congo the hardest-hit country reported more than 1,000 new mpox cases over the previous week.
In its latest update on the outbreak, the African Centers for Disease Control reported that as of Thursday, more than 21,300 suspected or confirmed cases and 590 deaths have been reported this year in 12 African countries.
Mpox belongs to the same family of viruses as smallpox but typically causes milder symptoms like fever, chills and body aches. It mostly spreads through close skin-to-skin contact, including sexual intercourse. People with more serious cases can develop lesions on the face, hands, chest and genitals.
About 4,000 more mpox cases were reported in Africa last week, mostly from the Democratic Republic of the Congo (DRC), the head of Africa Centres for Disease Control and Prevention (Africa CDC) said yesterday.
In another development, Nigeria yesterday received 10,000 mpox vaccine doses, becoming the first country to receive the vaccine, the World Health Organization (WHO) Nigeria office said in a statement.
At atelebriefing yesterday, Africa CDC Director-General Jean Kaseya, MD, MPH, said the outbreak is increasing, with 22,863 cases reported since the first of the year, up about 4,000 from the previous week. Deaths rose by 81 last week, putting the regions fatality count at 622.
One more countryGabonrecently reported its first case, lifting the number of affected countries to 13.
Earlier this week, the UN Refugee Agency (UNHCR)warned that the expanding mpox outbreak could be devastating for refugees and displaced communities in the DRC and other African countries. At a briefing, the group said at least 42 suspected cases have been reported in refugee populations in the DRCs South Kivu province. The group said conflict-affected provinces in the DRC host most of the countrys 7.3 million internally displaced people, which may mean the groups are cut off from humanitarian assistance.
Kaseya said cases are still increasing, but officials know that surveillance is still weak and that the case counts likely underestimate the disease burden. He also said officials know there is a data quality issue and said Africa CDC is deploying 72 epidemiologists to affected countries to get a better idea of where and how mpox is spreading.
Over the past week, Africa CDC officials have met with government heads from the DRC, as well as with international response partners, Kaseya said, adding that the DRCs commitment to battling the outbreak is clear and that the group is heartened by mpox vaccine donations that have already come from Europe; the United States; Gavi, the Vaccine Alliance; and other partners. Talks are under way with other donors.
The WHOs Nigeria office said the mpox vaccine doses it received, Jynneos made by Bavarian Nordic, will be rolled out in five states with the highest mpox burden. Nigerian regulators had already granted emergency use authorization for the vaccine.
Nigeria has reported mpox for several years, with cases that peaked in 2022. As of August 10, the country this year has reported 786 cases, 39 of them confirmed. None were fatal.
Muhammad Ali Pate, MD, MBA, MS, Nigerias health minister, said, We are pleased to receive this modest initial donation of the mpox vaccine which is safe and efficacious. We will continue to strengthen surveillance and be vigilant to prevent and control mpox. We urge the global health community to expand access to vaccines.
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Globally, the multi-country outbreak of mpox has led to 116 countries and territories in all WHO regions reporting 99 176 confirmed cases and 208 deaths (CFR 0.2%) between May 2022 and June 2024. The situation in the Democratic Republic of the Congo, linked to Clade I MPXV, has continued to evolve with cases rising steadily since late 2022 and has now become particularly concerning. This increased case reporting is driven by two concomitant outbreaks, including (1) outbreaks in historically endemic parts of the Democratic Republic of the Congo, affecting primarily children, and (2) a rapidly expanding outbreak of a new strain of MPXV clade I named clade Ib which like IIb appears to be spreading predominantly through sexual networks, expanding geographically in eastern provinces of the Democratic Republic of the Congo, and now also affecting neighbouring countries.
On 13 August 2024, Africa CDCs declared Mpox as a Public Health Emergency of Continental Security. This declaration aims to galvanize political leadership and engagement among AU Heads of State and Government, facilitating the rapid mobilisation of essential financial and technical resources to control the outbreak.
The Director-General of the World Health Organization (WHO), having concurred with the advice offered by the International Health Regulations (2005) (IHR or Regulations) Emergency Committee regarding the upsurge of mpox 2024 during its first meeting, held on 14 August 2024, has determined, on the same date, that the ongoing upsurge of mpox in the Democratic Republic of the Congo and a growing number of countries in Africa constitutes a public health emergency of international concern (PHEIC) under the provisions of the International Health Regulations.
This Research Response Conference is a pivotal gathering aimed at addressing the urgent global challenge posed by the mpox virus. This conference is designed to foster a collaborative and open environment where researchers, public health officials, and stakeholders from affected countries can take the lead in shaping the research agenda.
Our collective goal is to align research efforts with outbreak response strategies to effectively mitigate morbidity and mortality, halt transmission, and advance the development of vaccines, diagnostics, and therapeutics to prevent future outbreaks.
The World Health Organization (WHO) today announced the launch of a preparedness strategy and response plan to contain a mpox outbreak rapidly spreading in African countries, with two related cases recently reported in Sweden and Thailand.
The plan, which covers the next 6 months, also includes a more fleshed-out price tag of $135 million, for which the WHO will soon launch a funding appeal.
In a speech today at a meeting of the WHO regional committee for Africa, WHO Director-General Tedros Adhanom Ghebreyesus, PhD, said the plan hinges on comprehensive surveillance and response, minimizing zoonotic transmission, empowering communities to take an active role, and advancing research on and equitable access to vaccines and other countermeasures.
The plan also supplements recently published temporary recommendations from the WHOs emergency committee and standing recommendations for the earlier spread of the clade 2 mpox virus.
Cases in the Democratic Republic of the Congo (DRC), the main hot spot, have topped 18,000 this year, Tedros said, noting that cases are already above the record level in 2023.
Responding to each of these outbreaks, and bringing them under control, will require a complex, comprehensive, and coordinated international response.
So far, 220 cases of the new clade 1b virus, first seen in the DRC, have been reported in four of the DRCs neighbors that had never reported cases before. He said other clades have been reported in other DRC regions, as well as other African nations.
"It's a complex and dynamic picture, and responding to each of these outbreaks, and bringing them under control, will require a complex, comprehensive, and coordinated international response," he said.
Tedros said the WHO on August 23 received information from one vaccine manufacturer to allow consideration for emergency use listing (EUL), which he said could be issued in the next 3 weeks.
"In the meantime, I have given the green light to Gavi and UNICEF to proceed with procurement of vaccines, pending the EUL decision," he added.
The response plan said strategic vaccine efforts have a goal of interrupting transmission chains and will focus on people at greatest risk, including close contacts of recent cases and healthcare workers.
In other vaccine developments, Germany became the latest country to offer vaccine doses to the African region. Christoph Retzlaff, who directs African diplomacy for Germany, said on X that, as a first step, the country will send 100,000 doses to affected African countries. Media reports said the doses will come from Germany's military stockpile and that Germany will also provide financial resources.
The World Health Organization (WHO) today launched a global Strategic Preparedness and Response Plan to stop outbreaks of human-to-human transmission of mpox through coordinated global, regional, and national efforts. This follows the declaration of a public health emergency of international concern by the WHO Director-General on 14 August.
The current plan is subject to inputs by Member States, who were briefed on the plan on Friday, 23 August.
The plan covers the six-month period of September 2024-February 2025, envisioning a US$135 million funding need for the response by WHO, Member States, partners including Africa Centres for Disease Control and Prevention (Africa CDC), communities, and researchers, among others.
A funding appeal for what WHO needs to deliver on the plan will be launched shortly.
The plan, which builds on the temporary recommendations and standing recommendations issued by the WHO Director-General, focuses on implementing comprehensive surveillance, prevention, readiness and response strategies; advancing research and equitable access to medical countermeasures like diagnostic tests and vaccines; minimizing animal-to-human transmission; and empowering communities to actively participate in outbreak prevention and control.
Strategic vaccination efforts will focus on individuals at the highest risk, including close contacts of recent cases and healthcare workers, to interrupt transmission chains.
At the global-level, the emphasis is on strategic leadership, timely evidence-based guidance, and access to medical countermeasures for the most at-risk groups in affected countries.
WHO is working with a broad range of international, regional, national and local partners and networks to enhance coordination across key areas of preparedness, readiness and response. This includes engagement with the ACT-Accelerator Principals group; the Standing Committee on Health Emergency Prevention, Preparedness and Response; the R&D Blueprint for Epidemics; and the interim Medical Counter Measures Network (i-MCM Net).
The WHO R&D Blueprint, along with Africa CDC, Coalition for Epidemic Preparedness Innovations (CEPI) and National Institute of Allergy and Infectious Diseases, will host a virtual scientific conference on 29-30 August 2024 to align mpox research with outbreak control goals.
The mpox outbreaks in the Democratic Republic of the Congo and neighbouring countries can be controlled, and can be stopped, said Dr Tedros Adhanom Ghebreyesus, WHO Director-General. Doing so requires a comprehensive and coordinated plan of action between international agencies and national and local partners, civil society, researchers and manufacturers, and our Member States. This SPRP provides that plan, based on the principles of equity, global solidarity, community empowerment, human rights, and coordination across sectors.
WHO headquarters and regional offices have established incident management support teams to lead preparedness, readiness and response activities, and are significantly scaling up staff in affected countries.
Within the Africa Region, where need is greatest, the WHO Regional Office for Africa (AFRO) in collaboration with Africa CDC, will jointly spearhead the coordination of mpox response efforts. WHO AFRO and Africa CDC have agreed on a one-plan, one-budget approach as part of the Africa Continental Mpox Strategic Preparedness and Response Plan, currently under preparation.
At the national and sub-national level, health authorities will adapt strategies in response to current epidemiological trends.
Analyzed data and model fitting
We identified 7 publications including at least one case with lesion samples meeting the inclusion criteria, and a total of 90 mpox cases (seesection Methods). All cases were symptomatic, and most of them were reported in Europe. To standardize the collected data, we converted the reported cycle threshold values to viral load (copies/ml) using the conversion formula proposed in a previous study31 (Supplementary Table1). We then fitted a viral clearance model to the longitudinal viral load data from lesion samples (Supplementary Fig.1a and Supplementary Fig.2). Estimated parameters suggested a median viral load of 7.7 log10 copies/ml (95% CI: 7.38.2) at symptom onset and a median viral clearance rate of 0.36 day1 (95% CI: 0.240.44), respectively. Using these parameters, duration of infectiousness was estimated: we first assumed a threshold value for infectiousness as 6.0 log10 copies/ml based on data on viral replication in cell culture23,32,33, and the duration of infectiousness was estimated to be 10.9 days (95% CI: 7.321.6) following the onset of symptoms. Additionally, a prolonged duration of viral shedding was estimated: the viral load dropped below the limit of detection of a PCR test (2.9 log10 copies/ml) 30.9 days (95% CI: 23.450.6) after symptom onset (Supplementary Fig.1b). This finding is consistent with previous studies suggesting the persistent presence of mpox viruses in clinical specimens23,34.
The 90 analyzed mpox cases were stratified into two groups Group 1 and Group 2 (Fig.1ac), using the K-means clustering algorithm based on three estimated individual-level parameters: the viral load at symptom onset, the total amount of virus excreted between symptom onset and the end of shedding, and the duration of viral shedding (see Supplementary Note2). Group 1 had a lower viral load at symptom onset and faster viral clearance, whereas Group 2 showed a higher viral load at symptom onset and slower viral clearance. As a result, the estimated duration of infectiousness in Group 2 was longer than in Group 1 (Fig.1c and Supplementary Fig.1b). To compare the viral dynamics between the two groups, we conducted statistical tests: Individuals in Group 2 had significantly higher viral loads at symptom onset than individuals in Group 1 ((p=5.7times {10}^{-10}) from the MannWhitney test). Viral clearance was significantly slower in Group 2 than in Group 1 ((p=2.1times {10}^{-9}) from the MannWhitney test). Also, individuals in Group 2 had a larger area under the viral load curve (AUC) ((p=4.6times {10}^{-11}) from the MannWhitney test). Thus, Groups 1 and 2 were characterized as groups with low and high transmission potential, respectively (Fig.1d). To describe the difference in timing of viral clearance, we also reconstructed the probability of virus being detectable over time by using the model with estimated parameters for each group (Fig.1e). In both stratified groups, the probability was greater than 90% at 3 weeks after symptom onset. However, in the total group (i.e., a group of all analyzed cases), the probability dropped to 69.9% (95% CI: 67.073.2) at 4 weeks after symptom onset, which is the upper bound of the isolation period recommended by the CDC and ECDC19,25. The probability in Group 1 at 4 weeks after symptom onset was 61.6% (95% CI: 58.264.8), whereas the corresponding probability in Group 2 was 94.6% (95% CI: 93.196.0).
a Results of K-means clustering of mpox cases based on viral load at symptom onset, area under the viral load curve (AUC), i.e., the total amount of virus shed over time, and duration of viral shedding using estimated individual parameters. Data points indicate individuals and are colored based on the group that each individual is in. Principal component analysis (PCA) was used to visualize the clusters in two dimensions. Groups 1 and 2 comprise 71 and 19 mpox cases, respectively. b Stratified viral load data points measured in lesion samples. The cross represents data points where the viral load was below the limit of detection. c Reconstructed individual viral load trajectories in each group. The horizontal dashed line means the assumed infectiousness threshold. d Comparison between groups of: viral load at symptom onset (left panel); duration of viral shedding (middle panel); and area under viral load curve (right panel), respectively. The box-and-whisker plots show the medians (50th percentile; bold lines), interquartile ranges (25th and 75th percentiles; boxes), and 2.5th to 97.5th percentile ranges (whiskers). The sizes of Group 1 and Group 2 are 71 and 19 cases, respectively. Using the two-sided MannWhitney test, statistically significant differences between the two groups were found for viral load at symptom onset (({p},{mbox{value}}=5.7times {10}^{-10})), duration of viral shedding (({p},{mbox{value}}=2.1times {10}^{-9})), and area under viral load curve (({p},{mbox{value}}=4.6times {10}^{-11})). Group 1 and Group 2 represent cases with low and high risk of transmission, respectively. e Viral clearance in each group. Probability of detectable virus after symptom onset for each group (left panel). The solid lines and shaded regions indicate means and 95% confidence intervals, respectively. The dashed lines and dotted lines stand for probabilities at 3 and 4 weeks after symptom onset, respectively. Bar plots represent the probabilities for 3 weeks (right upper panel) and 4 weeks (right lower panel) after symptom onset, respectively. The centers and error bars indicate means and 95% confidence intervals, respectively. Note that the estimated probabilities are based on 100 independent simulations.
Under the estimated viral dynamics, we compared three types of rules for ending the isolation of individuals with mpox: a symptom-based rule, a fixed-duration rule, and a testing-based rule. To assess the effectiveness of the three rules, we considered three metrics: (1) the risk of prematurely ending isolation, (2) the average estimated infectious period after ending isolation (where this period was defined to be zero for individuals who are no longer infectious at the time of ending isolation), and (3) the average estimated duration for which individuals were isolated unnecessarily after the end of their infectious period (which could be positive or negative). Whether an individual was infectious or not was ascertained based on an assumed threshold viral load value (see section Methods).
With these metrics, we first evaluated the current symptom-based isolation guideline (i.e., patients remain isolated until their skin lesions have cleared), accounting for variations in the timing of lesion clearance between individuals. We estimated distributions of the timing of lesion clearance using data from 43 mpox patients describing the duration of lesion presence (see section Methods). As a result, the mean duration from symptom onset to lesion clearance was estimated to be 25.2 days (95% CI: 21.629.7). The median and interquartile range (IQR) were 23.2 days and 17.630.7 days, respectively. The estimated values were consistent with typical current isolation periods of 24 weeks18,19,25,26,27,28 (Supplementary Fig.3 and Supplementary Table.4). In the total group, the risk of prematurely ending isolation was estimated to be 8.8% (95% CI: 6.710.5) and Group 1 had a lower risk of 4.9% (95% CI: 3.86.1). In addition, both stratified groups yielded an average estimated infectious period after ending isolation of lower than 1 day. However, in Group 2, the risk of prematurely ending isolation was 25.7% (95% CI: 23.828.0) with a longer estimated infectious period after ending isolation of 1.6 days (95% CI: 1.41.8). The mean estimated duration for which individuals in the total group were isolated unnecessarily after the end of their infectious period was 12.1 days (95% CI: 11.612.8), whereas Groups 1 and 2 had unnecessary isolation periods of 13.5 days (95% CI: 13.014.1) and 6.6 days (95% CI: 5.97.3), respectively (Supplementary Fig.4).
Furthermore, to ensure isolation is ended safely, we considered an additional isolation period beyond the time of lesion clearance. To lower the risk of prematurely ending isolation below 5% and the estimated infectious period after ending isolation below 1 day, the total group and Group 2 required additional isolation periods of 3 and 10 days on average, respectively. However, no additional isolation periods were necessary for Group 1. The resulting unnecessarily prolonged isolation periods in the total group, Group 1, and Group 2 were estimated to be 15.1, 13.5, and 16.6 days on average, respectively (Fig.2a).
a Symptom-based rules. The vertical dotted lines mean the current symptom-based isolation guideline. The x-axis represents the additional isolation period from the current guideline. b Fixed-duration rules. The x-axis represents the fixed period of isolation. Left panels in both a and b show the risk of prematurely ending isolation for different isolation periods. The horizontal lines correspond to 5%. Estimated infectious period after ending isolation for different isolation periods (middle panels). The horizontal lines correspond to 1 day. The estimated period for which individuals are isolated unnecessarily after the end of their infectious period for different isolation periods (right panels). The squares and circles indicate the points with the lowest unnecessarily prolonged isolation period for which the following conditions are satisfied: i) the risk of prematurely ending isolation is lower than 5% and ii) the estimated infectious period after ending isolation is shorter than 1 day. The vertical dashed lines correspond to the optimal additional isolation period and the optimal fixed duration of isolation in the total group for symptom-based rules and fixed-duration rules, respectively. The solid lines and shaded regions in each panel indicate means and 95% confidence intervals, respectively. c Testing-based rules. The risk of prematurely ending isolation (first row of panels), the estimated infectious period after ending isolation (second row of panels), the estimated isolation period following the end of infectiousness (third row of panels), and the overall isolation period (fourth row of panels) are shown for different intervals between tests and numbers of consecutive tests indicating loss of infectiousness necessary to end isolation. PCR (polymerase chian reaction) tests (limit of detection ({{boldsymbol{=}}}) 2.9 log10 copies/ml) were used to measure viral load. The areas surrounded by solid lines are those with 5% or lower risk of prematurely ending isolation and with 1 day or shorter estimated infectious period after ending isolation, respectively. The triangles correspond to the points with the shortest estimated isolation period following the end of infectiousness for which both conditions noted above are satisfied. Color keys and symbols apply to all panels. Note that the estimated values are based on 100 independent simulations.
In our main analyses, we assumed that the presence or absence of symptoms was independent of viral dynamics. However, as a sensitivity analysis, we evaluated the current symptom-based rule for the total group under different assumed relationships between individual viral dynamics and the duration of lesion presence (see section Methods). The risk of ending isolation prematurely was lower when increased and/or prolonged viral shedding was assumed to be more strongly correlated with slower lesion clearancethe estimated risk under our baseline assumption (i.e., that lesion clearance is independent of viral shedding) can therefore be considered as an upper bound. This is because, if the presence of lesions is shown to be positively correlated with viral shedding, patients with fast lesion clearance could end isolation safely, and thus the estimated risk under such conditions would be lower than the baseline assumption. The unnecessarily prolonged isolation periods in this supplementary analysis were found to be comparable to those under the baseline setting and were lower than 2 weeks on average (Supplementary Fig.5).
Under a fixed-duration rule of ending isolation 3 weeks after symptom onset, the risk of ending isolation prematurely in the total group was estimated to be 5.4% (95% CI: 4.16.7). The average estimated duration for which individuals were isolated unnecessarily after the end of their infectious period was 8.3 days (95% CI: 8.08.6). Group 1 had a lower risk of ending isolation prematurely of 1.9% (95% CI: 1.02.9), and a longer unnecessary isolation period of 9.7 days (95% CI: 9.49.9). However, in Group 2, a higher risk of 25.7% (95% CI: 23.228.0) was estimated, with a shorter unnecessary isolation period of 2.8 days (95% CI: 2.43.1). To guarantee a risk of prematurely ending isolation below 5% and an estimated infectious period after ending isolation shorter than 1 day, we found that the total group, Group 1, and Group 2 needed to be isolated for 22, 19, and 29 days, respectively. In this case, the estimated duration for which individuals were isolated unnecessarily after the end of their infectious period was estimated to be 9.4, 7.7, and 10.8 days for the total group, Group 1, and Group 2, respectively (Fig.2b).
For symptom-based and fixed-duration rules, isolation of individuals with mpox ends after lesion clearance or fixed-time period following symptom onset, so the three metrics considered here are determined by the mean symptom duration or the predefined isolation period (Fig.2a, b). By contrast, a testing-based rule is dependent on both the time interval between tests and the exact criterion used for ending isolation (see section Methods). Under a criterion in which isolation ends following two consecutive PCR test results indicating loss of infectiousness with daily testing (similar to a criterion widely used for COVID-19)17, the total group had a risk of prematurely ending isolation of 52.2% (95% CI: 49.754.6), and the estimated infectious period after ending isolation was calculated to be 2.3 days (95% CI: 2.12.5). Similarly, high risks of prematurely ending isolation, accompanied with an estimated infectious period after ending isolation longer than 1 day, were estimated in the stratified groups (first-row and second-row panels in Fig.2c).
By varying the criteria (i.e., the required number of consecutive test results indicating loss of infectiousness and the time interval between tests), different testing-based isolation rules can be tested in terms of their effects on the three metrics. The risk of prematurely ending isolation and the estimated infectious period after ending isolation decreased with a longer interval between tests and with a larger number of consecutive test results indicating loss of infectiousness (first-row and second-row panels in Fig.2c), whereas the estimated duration for which individuals were isolated unnecessarily after the end of their infectious period increased (third-row panels in Fig.2c). Under the conditions that the risk of prematurely ending isolation is lower than 5% and the estimated infectious period after ending isolation is shorter than 1 day, the minimum value of the unnecessary isolation period in the total group was 7.4 days (95% CI: 7.17.7) with three consecutive test results indicating loss of infectiousness and an interval of 5 days between tests (purple triangles in Fig.2c). Correspondingly, an isolation period of 20.1 days (95% CI: 19.720.5) was required on average. On the other hand, under the same conditions, stricter rules were needed for Group 2: four consecutive test results indicating loss of infectiousness and an interval of 2 days between tests were needed to minimize the estimated duration for which individuals were isolated unnecessarily after the end of their infectious period to 8.4 days (95% CI: 8.08.7), with a mean isolation period of 26.6 days (95% CI: 26.027.0) (red triangles in Fig.2c).
To further evaluate the uncertainty in the test-based rule, we considered a different type of measurement error model (i.e., a proportional error model), where the error variance increases in proportional to the predicted mean viral load, and examined the corresponding difference in the total group as a sensitivity analysis (see section Methods). While the measurement error was constant in the main analysis (i.e., constant error model), the proportional error model described higher error variance near the assumed infectiousness threshold. As a result, a stricter optimal isolation rule was needed to lower the risk and the estimated infectious period after ending isolation below 5% and 1 day, respectively: four consecutive test results indicating loss of infectiousness and an interval of 3 days between tests. However, the minimized unnecessary period and corresponding optimal isolation period under the proportional error model were comparable to the constant error model (Supplementary Fig.6).
Additionally, whereas we focused on PCR testing in our main analyses, we conducted further analyses considering rapid antigen tests (RATs) to evaluate the effectiveness of using different test types when applying the testing-based rule. Under the testing-based rules using RATs, test results correspond to negative results (i.e., measured viral loads below a limit of detection) (see section Methods). When RATs with either high or low sensitivity were utilized in the testing-based rule, the optimal isolation periods on average were comparable with those under PCR testing. However, the optimal testing rules for ending isolation differed depending on RAT sensitivity: 2 consecutive negative results with 3-day intervals between tests were optimal for the high sensitivity RAT and 5 consecutive negative results with 3-day intervals between tests were optimal for the low sensitivity RAT. In both scenarios, a higher number of total tests was required to meet the specified conditions (i.e., the risk of prematurely ending isolation (le)5% and the estimated infectious period after ending isolation (le)1 day) (Supplementary Fig.7) than for PCR testing, since even high sensitivity RATs are typically much less sensitive than PCR tests (see Supplementary Note5 and Supplementary Fig.8). Additionally, RATs only provide qualitative test results (i.e. positive or negative), making it impossible to determine whether an individual who tests positive has a viral load that has fallen below the assumed infectiousness threshold.
To highlight the difference between the three isolation rules for each group, we compared the three types of rule by computing the optimal rules in which the estimated isolation period following the end of infectiousness is minimized while ensuring that the risk of prematurely ending isolation is less than 5% and the estimated infectious period after ending isolation is less than 1 day (squares, circles, and triangles in Fig.2). In the total group, the optimized symptom-based (i.e., current guideline (+)3 days), fixed-duration, and testing-based rules gave isolation periods of 28.3, 22, and 20.1 days, resulting in minimized unnecessary isolation periods of 15.1, 9.4, and 7.4 days on average, respectively (Fig.3). In particular, compared to the current (non-optimized) symptom-based rule, the other two optimized rules involved shorter isolation periods and reduced unnecessarily prolonged isolation periods. In Group 2, the testing-based rule led to an unnecessary isolation period that was 8.2 and 2.4 days shorter than the symptom-based and fixed-duration rules, respectively. The testing-based rule in Group 1 yielded an unnecessary isolation period of 7.1 days shorter than the symptom-based rule, whereas it was comparable to the fixed-duration rule. However, compared with the other two rules in the total group, the testing-based rule in Group 1 could reduce the unnecessary isolation period to 17.7 days, with the optimal isolation period of 6.4 days.
The filled squares, circles, and triangles represent symptom-based, fixed-duration, and testing-based rules, respectively. Each symbol represents the mean length of isolation using the rule that minimizes unnecessarily prolonged isolation under the conditions that the risk of prematurely ending isolation is less than 5% and the estimated infectious period after ending isolation is less than 1 day. Note that for testing-based rules, the interval between tests and the number of consecutive tests indicating loss of infectiousness necessary to end isolation were chosen to minimize the unnecessarily prolonged isolation period. The vertical lines indicate the optimized isolation periods of three isolation rules for the total group. The unfilled square with outline indicates the current (non-optimized) symptom-based rule for the total group.
In addition, to assess the effectiveness of the testing-based rule, we examined the difference between the testing-based rule and the other two rules in the total group. The considered conditions for this assessment were; three consecutive test results indicating loss of infectiousness and a 5-day interval between tests for the testing-based rule (Fig.2c), the current isolation guideline (i.e., the estimated duration of lesion presence) for the symptom-based rule, and the 22-day isolation period for the fixed-duration rule (Fig.2a, b). Compared with symptom-based and fixed-duration rules, 63.2% (95% CI: 60.866.0) and 63.5% (95% CI: 60.665.4) of the total group could reduce their isolation periods using the testing-based rule, respectively (Supplementary Fig.9a). The mean isolation period was shortened by 10.8 and 5.5 days compared to symptom-based and fixed-duration rules, respectively, and the average unnecessarily prolonged isolation period was also effectively reduced (Supplementary Fig.9b, c). In these cases, the total number of tests required for ending isolation in the testing-based rule was estimated to be from 3 to 7 times (Supplementary Fig.9d).
As a sensitivity analysis, we varied the assumed infectiousness threshold and investigated the corresponding difference in the estimated period for which individuals were isolated unnecessarily after the end of their infectious period between the three rules (Supplementary Fig.10). When the assumed infectiousness threshold is higher, the corresponding estimated infectious period becomes shorter, leading to a shorter required isolation period and shorter period of unnecessary isolation given the same acceptable risk. Our analysis showed that a higher assumed infectiousness threshold resulted in smaller differences between the fixed-duration and testing-based rules for each stratified group, which was consistent with our previous findings for COVID-199. On the other hand, simulations for the symptom-based rule in the total group suggested that the current guideline would lead to safer ending isolation but longer unnecessary isolation periods if the assumed infectiousness threshold value was increased.
We used an assumed infectiousness threshold of the viral load (6.0 log10 copies/ml) as a cut-off value for assessing isolation rules in the main analysis; however, other metrics for the risk of prematurely ending isolation could also be considered. To demonstrate this, we estimated the average area under the viral load curve (AUC) following the end of isolation for the total group under the different isolation rules, and compared the estimated values with the AUC without isolation (see Supplementary Note6). Without any isolation, the average AUC was estimated to be 108.5 copies/mldays (95% CI: 108.4108.6). On the other hand, the estimates of average AUC after ending isolation were 106.3 copies/mldays (95% CI: 106.1106.5), 106.0 copies/mldays (95% CI: 105.8106.1), and 105.8 copies/mldays (95% CI: 105.7105.9) under the current isolation guideline (i.e., the estimated duration of symptoms) for the symptom-based rule, the 22-day isolation period for the fixed-duration rule, and three consecutive test results indicating loss of infectiousness and a 5-day interval between tests for the testing-based rule, respectively. Compared to the case of no isolation, the average AUC was reduced by more than 95% under all three isolation rules, with the optimized testing-based rule giving the greatest reduction in the AUC (Supplementary Fig.11). This indicates that the risk of prematurely ending isolation can be limited through those isolation rules.
Additionally, to highlight the necessity of the optimal isolation strategy (i.e., three consecutive test results indicating loss of infectiousness and a 5-day interval between tests) for the testing-based rules, we compared its average AUC to one under the other testing strategy. Since the mpox viral load continuously decreases over time since symptom onset, only one test result may be considered sufficient to guarantee the loss of infectiousness. However, this strategy may miss the ongoing infectiousness due to the measurement error (Supplementary Fig.12a), whereas the optimal isolation strategy may end isolation more safely (Supplementary Fig.12b). The average AUC under the strategy with one test result indicating loss of infectiousness and a 5-day interval between tests was estimated to be 107.8 copies/mldays (95% CI: 107.7(-)107.9), much higher than one under the optimal testing strategy (Supplementary Fig.12c).
As a sensitivity analysis, we considered an alternative two-phase exponential decay model35, estimated the viral dynamics, and assessed the effectiveness of different isolation rules. In this additional analysis, to ensure that the parameters were identifiable, we used data from 30 cases (out of 90 cases with lesion samples) for which the viral load in lesion samples was recorded at four or more time points (see Supplementary Note7). Compared to the baseline model (one-phase exponential decay model), the two-phase model indicated a higher viral load at symptom onset with a faster clearance in the first phase but with a slower clearance in the second phase (Supplementary Fig.13a, Supplementary Fig.14, and Supplementary Table5), resulting in a longer estimated duration of infectiousness (p = 2.1 104 from the Mann-Whitney test) (Supplementary Fig.13b). However, there was no significant difference in the duration of viral shedding between the baseline model and the two-phase exponential decay model (Supplementary Fig.13c). For symptom-based and fixed-duration isolation rules under the two-phase exponential decay model, longer isolation periods on average were needed for ending isolation than using the baseline model. On the other hand, under the testing-based rules, the required isolation period was comparable with the baseline model (Supplementary Fig.13d). Consequently, in the two-phase exponential decay model, the testing-based rules again substantially reduced the unnecessary duration of isolation, with shorter required isolation periods than under the symptom-based and fixed-duration rules.
To demonstrate that lesion samples are suitable for designing isolation rules, we compared the viral dynamics that we inferred using lesion samples to analogous results obtained using other samples. Specifically, we used longitudinal viral load data measured in upper respiratory tract, blood, and semen samples from the same mpox cases to estimate mpox virus dynamics in those samples (Supplementary Table1, Supplementary Table2, Supplementary Fig.15a, and Supplementary Fig.16). Following symptom onset, other samples exhibited lower viral loads compared with lesion samples. For example, at the optimal ending isolation period of 22 days under fixed-duration rules, the viral load in lesion samples was substantially higher than in other samples (Supplementary Fig.15b). Moreover, we compared the predicted infectiousness in lesion samples and other samples by estimating the proportion of individuals who remained infectious on day 22 after symptom onset. Around 3% of individuals were estimated to be infectious when lesion samples were used, whereas the viral load never exceeded the assumed infectiousness threshold for the other samples (Supplementary Fig.15c). This suggests that infectious individuals with mpox may be missed if we implement a testing-based rule with samples other than lesion samples.
