A combination of annual and nonannual forces drive respiratory disease in the tropics.

INTRODUCTION: It is well known that influenza and other respiratory viruses are wintertime-seasonal in temperate regions. However, respiratory disease seasonality in the tropics is less well understood. In this study, we aimed to characterise the seasonality of influenza-like illness (ILI) and influenza virus in Ho Chi Minh City, Vietnam. METHODS: We monitored the daily number of ILI patients in 89 outpatient clinics from January 2010 to December 2019. We collected nasal swabs and tested for influenza from a subset of clinics from May 2012 to December 2019. We used spectral analysis to describe the periodic signals in the system. We evaluated the contribution of these periodic signals to predicting ILI and influenza patterns through lognormal and gamma hurdle models. RESULTS: During 10 years of community surveillance, 66 799 ILI reports were collected covering 2.9 million patient visits; 2604 nasal swabs were collected, 559 of which were PCR-positive for influenza virus. Both annual and nonannual cycles were detected in the ILI time series, with the annual cycle showing 8.9% lower ILI activity (95% CI 8.8% to 9.0%) from February 24 to May 15. Nonannual cycles had substantial explanatory power for ILI trends (ΔAIC=183) compared with all annual covariates (ΔAIC=263) in lognormal regression. Near-annual signals were observed for PCR-confirmed influenza but were not consistent over time or across influenza (sub)types. The explanatory power of climate factors for ILI and influenza virus trends was weak. CONCLUSION: Our study reveals a unique pattern of respiratory disease dynamics in a tropical setting influenced by both annual and nonannual drivers, with influenza dynamics showing near-annual periodicities. Timing of vaccination campaigns and hospital capacity planning may require a complex forecasting approach.

A combination of annual and nonannual forces drive respiratory disease in the tropics.

Background: It is well known that influenza and other respiratory viruses are wintertime-seasonal in temperate regions. However, respiratory disease seasonality in the tropics remains elusive. In this study, we aimed to characterize the seasonality of influenza-like illness (ILI) and influenza virus in Ho Chi Minh City (HCMC), Vietnam. Methods: We monitored the daily number of ILI patients in 89 outpatient clinics from January 2010 to December 2019. We collected nasal swabs and tested for influenza from a subset of clinics from May 2012 to December 2019. We used spectral analysis to describe the periodicities in the system. We evaluated the contribution of these periodicities to predicting ILI and influenza patterns through lognormal and gamma hurdle models. Findings: During ten years of community surveillance, 66,799 ILI reports were collected covering 2.9 million patient visits; 2604 nasal swabs were collected 559 of which were PCR-positive for influenza virus. Both annual and nonannual cycles were detected in the ILI time series, with the annual cycle showing 8.9% lower ILI activity (95% CI: 8.8%-9.0%) from February 24 to May 15. Nonannual cycles had substantial explanatory power for ILI trends (ΔAIC = 183) compared to all annual covariates (ΔAIC = 263). Near-annual signals were observed for PCR-confirmed influenza but were not consistent along in time or across influenza (sub)types. Interpretation: Our study reveals a unique pattern of respiratory disease dynamics in a tropical setting influenced by both annual and nonannual drivers. Timing of vaccination campaigns and hospital capacity planning may require a complex forecasting approach.

Supply chains create global benefits from improved vaccine accessibility.

Ensuring a more equitable distribution of vaccines worldwide is an effective strategy to control global pandemics and support economic recovery. We analyze the socioeconomic effects - defined as health gains, lockdown-easing effect, and supply-chain rebuilding benefit - of a set of idealized COVID-19 vaccine distribution scenarios. We find that an equitable vaccine distribution across the world would increase global economic benefits by 11.7% ($950 billion per year), compared to a scenario focusing on vaccinating the entire population within vaccine-producing countries first and then distributing vaccines to non-vaccine-producing countries. With limited doses among low-income countries, prioritizing the elderly who are at high risk of dying, together with the key front-line workforce who are at high risk of exposure is projected to be economically beneficial (e.g., 0.9%~3.4% annual GDP in India). Our results reveal how equitable distributions would cascade more protection of vaccines to people and ways to improve vaccine equity and accessibility globally through international collaboration.

How to avoid a local epidemic becoming a global pandemic.

Here, we combine international air travel passenger data with a standard epidemiological model of the initial 3 mo of the COVID-19 pandemic (January through March 2020; toward the end of which the entire world locked down). Using the information available during this initial phase of the pandemic, our model accurately describes the main features of the actual global development of the pandemic demonstrated by the high degree of coherence between the model and global data. The validated model allows for an exploration of alternative policy efficacies (reducing air travel and/or introducing different degrees of compulsory immigration quarantine upon arrival to a country) in delaying the global spread of SARS-CoV-2 and thus is suggestive of similar efficacy in anticipating the spread of future global disease outbreaks. We show that a lesson from the recent pandemic is that reducing air travel globally is more effective in reducing the global spread than adopting immigration quarantine. Reducing air travel out of a source country has the most important effect regarding the spreading of the disease to the rest of the world. Based upon our results, we propose a digital twin as a further developed tool to inform future pandemic decision-making to inform measures intended to control the spread of disease agents of potential future pandemics. We discuss the design criteria for such a digital twin model as well as the feasibility of obtaining access to the necessary online data on international air travel.

Synergistic interventions to control COVID-19: Mass testing and isolation mitigates reliance on distancing.

Stay-at-home orders and shutdowns of non-essential businesses are powerful, but socially costly, tools to control the pandemic spread of SARS-CoV-2. Mass testing strategies, which rely on widely administered frequent and rapid diagnostics to identify and isolate infected individuals, could be a potentially less disruptive management strategy, particularly where vaccine access is limited. In this paper, we assess the extent to which mass testing and isolation strategies can reduce reliance on socially costly non-pharmaceutical interventions, such as distancing and shutdowns. We develop a multi-compartmental model of SARS-CoV-2 transmission incorporating both preventative non-pharmaceutical interventions (NPIs) and testing and isolation to evaluate their combined effect on public health outcomes. Our model is designed to be a policy-guiding tool that captures important realities of the testing system, including constraints on test administration and non-random testing allocation. We show how strategic changes in the characteristics of the testing system, including test administration, test delays, and test sensitivity, can reduce reliance on preventative NPIs without compromising public health outcomes in the future. The lowest NPI levels are possible only when many tests are administered and test delays are short, given limited immunity in the population. Reducing reliance on NPIs is highly dependent on the ability of a testing program to identify and isolate unreported, asymptomatic infections. Changes in NPIs, including the intensity of lockdowns and stay at home orders, should be coordinated with increases in testing to ensure epidemic control; otherwise small additional lifting of these NPIs can lead to dramatic increases in infections, hospitalizations and deaths. Importantly, our results can be used to guide ramp-up of testing capacity in outbreak settings, allow for the flexible design of combined interventions based on social context, and inform future cost-benefit analyses to identify efficient pandemic management strategies.

Prioritizing vaccination by age and social activity to advance societal health benefits in Norway: a modelling study.

BACKGROUND: Vaccination has the proven effectiveness in reducing disease burden. As the emergency program is moving towards completion in many countries, there is a new urgency to appropriately assess the societal health benefits in both the near and longer term. METHODS: Using an age-structured mathematical infection model, we evaluate the gains achievable by adopting the ongoing and the possible alternative vaccination strategies to reduce COVID-19 infections in the current pandemic as well as during the future successive waves in Norway. We explicitly consider three allocation strategies, with single focus group on either (i) the older age groups at high risk of dying or (ii) the core-sociable groups at high risk of exposure and onwards transmission, versus strategies focusing on both groups by (iii) switching among the high-risk to the core-sociable. FINDINGS: Following the Norwegian Institute of Public Health (FHI) schedule, we estimate that allocating vaccines in an age-descending order may reduce around one-third of the infections; while strategy considering age-specific sociability may contribute to an additional ∼10% fewer infections. INTERPRETATION: A key insight of our study is that prioritizing the high-risk and core-sociable groups may maximize the benefit due to both direct and indirect protections, and thus achieving the larger societal health benefits. Our analyses provides a quantitative tool to planning of future campaigns for Scandinavian and other countries with comparable infection-fatality ratios, demographies and public health infrastructure. FUNDING: Research Council of Norway and the Penn State University.

A general model for the demographic signatures of the transition from pandemic emergence to endemicity.

Anticipating the medium- and long-term trajectory of pathogen emergence has acquired new urgency given the ongoing COVID-19 pandemic. For many human pathogens, the burden of disease depends on age and previous exposure. Understanding the intersection between human population demography and transmission dynamics is therefore critical. Here, we develop a realistic age-structured mathematical model that integrates demography, social mixing, and immunity to establish a plausible range for future age incidence and mortality. With respect to COVID-19, we identify a plausible transition in the age structure of risks once the disease reaches seasonal endemism across a range of immunity durations and relative severity of primary versus subsequent reinfections. We train the model using diverse real-world demographies and age-structured mixing to bound expectations for changing age incidence and disease burden. The mathematical framework is flexible and can help tailor mitigation strategies in countries worldwide with varying demographies and social mixing patterns.

Switching vaccination among target groups to achieve improved long-lasting benefits.

The development of vaccines has opened a way to lower the public health and societal burden of COVID-19 pandemic. To achieve sustainable gains in the long term, switching the vaccination from one target group to a more diverse portfolio should be planned appropriately. We lay out a general mathematical framework for comparing alternative vaccination roll-out strategies for the year to come: single focus groups: (i-a) the high-risk older age groups and (i-b) the core-sociable groups; and two focus groups: (ii-a) mixed vaccination of both the high-risk and core-sociable groups simultaneously and (ii-b) cyclic vaccination switching between groups. Featuring analyses of all relevant data including age pyramids for 15 representative countries with diverse social mixing patterns shows that mixed strategies that result in both direct and indirect protection of high-risk groups may be better for the overall societal health impact of COVID-19 vaccine roll-out. Of note, over time switching the priority from high-risk older age groups to core-sociable groups responsible for heightened circulation and thus indirect risk may be increasingly advantageous.

The ecological dynamics of the coronavirus epidemics during transmission from outside sources when R 0 is successfully managed below one.

Since COVID-19 spread globally in early 2020 and was declared a pandemic by the World Health Organization (WHO) in March, many countries are managing the local epidemics effectively through intervention measures that limit transmission. The challenges of immigration of new infections into regions and asymptomatic infections remain. Standard deterministic compartmental models are inappropriate for sub- or peri-critical epidemics (reproductive number close to or less than one), so individual-based models are often used by simulating transmission from an infected person to others. However, to be realistic, these models require a large number of parameters, each with its own set of uncertainties and lack of analytic tractability. Here, we apply stochastic age-structured Leslie theory with a long history in ecological research to provide some new insights to epidemic dynamics fuelled by external imports. We model the dynamics of an epidemic when R 0 is below one, representing COVID-19 transmission following the successful application of intervention measures, and the transmission dynamics expected when infections migrate into a region. The model framework allows more rapid prediction of the shape and size of an epidemic to improve scaling of the response. During an epidemic when the numbers of infected individuals are rapidly changing, this will help clarify the situation of the pandemic and guide faster and more effective intervention.

Strategic testing approaches for targeted disease monitoring can be used to inform pandemic decision-making.

More than 1.6 million Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) tests were administered daily in the United States at the peak of the epidemic, with a significant focus on individual treatment. Here, we show that objective-driven, strategic sampling designs and analyses can maximize information gain at the population level, which is necessary to increase situational awareness and predict, prepare for, and respond to a pandemic, while also continuing to inform individual treatment. By focusing on specific objectives such as individual treatment or disease prediction and control (e.g., via the collection of population-level statistics to inform lockdown measures or vaccine rollout) and drawing from the literature on capture-recapture methods to deal with nonrandom sampling and testing errors, we illustrate how public health objectives can be achieved even with limited test availability when testing programs are designed a priori to meet those objectives.

Associations between changes in population mobility in response to the COVID-19 pandemic and socioeconomic factors at the city level in China and country level worldwide: a retrospective, observational study.

BACKGROUND: Until broad vaccination coverage is reached and effective therapeutics are available, controlling population mobility (ie, changes in the spatial location of a population that affect the spread and distribution of pathogens) is one of the major interventions used to reduce transmission of SARS-CoV-2. However, population mobility differs across locations, which could reduce the effectiveness of pandemic control measures. Here we assess the extent to which socioeconomic factors are associated with reductions in population mobility during the COVID-19 pandemic, at both the city level in China and at the country level worldwide. METHODS: In this retrospective, observational study, we obtained anonymised daily mobile phone location data for 358 Chinese cities from Baidu, and for 121 countries from Google COVID-19 Community Mobility Reports. We assessed the intra-city movement intensity, inflow intensity, and outflow intensity of each Chinese city between Jan 25 (when the national emergency response was implemented) and Feb 18, 2020 (when population mobility was lowest) and compared these data to the corresponding lunar calendar period from the previous year (Feb 5 to March 1, 2019). Chinese cities were classified into four socioeconomic index (SEI) groups (high SEI, high-middle SEI, middle SEI, and low SEI) and the association between socioeconomic factors and changes in population mobility were assessed using univariate and multivariable linear regression. At the country level, we compared six types of mobility (residential, transit stations, workplaces, retail and recreation, parks, and groceries and pharmacies) 35 days after the implementation of the national emergency response in each country and compared these to data from the same day of the week in the baseline period (Jan 3 to Feb 6, 2020). We assessed associations between changes in the six types of mobility and the country's sociodemographic index using univariate and multivariable linear regression. FINDINGS: The reduction in intra-city movement intensity in China was stronger in cities with a higher SEI than in those with a lower SEI (r=-0·47, p<0·0001). However, reductions in inter-city movement flow (both inflow and outflow intensity) were not associated with SEI and were only associated with government control measures. In the country-level analysis, countries with higher sociodemographic and Universal Health Coverage indexes had greater reductions in population mobility (ie, in transit stations, workplaces, and retail and recreation) following national emergency declarations than those with lower sociodemographic and Universal Health Coverage indexes. A higher sociodemographic index showed a greater reduction in mobility in transit stations (r=-0·27, p=0·0028), workplaces (r=-0·34, p=0·0002), and areas retail and recreation (rxs=-0·30, p=0·0012) than those with a lower sociodemographic index. INTERPRETATION: Although COVID-19 outbreaks are more frequently reported in larger cities, our analysis shows that future policies should prioritise the reduction of risks in areas with a low socioeconomic level-eg, by providing financial assistance and improving public health messaging. However, our study design only allows us to assess associations, and a long-term study is needed to decipher causality. FUNDING: Chinese Ministry of Science and Technology, Research Council of Norway, Beijing Municipal Science & Technology Commission, Beijing Natural Science Foundation, Beijing Advanced Innovation Program for Land Surface Science, National Natural Science Foundation of China, China Association for Science and Technology.

Immunological characteristics govern the transition of COVID-19 to endemicity.

We are currently faced with the question of how the severity of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may change in the years ahead. Our analysis of immunological and epidemiological data on endemic human coronaviruses (HCoVs) shows that infection-blocking immunity wanes rapidly but that disease-reducing immunity is long-lived. Our model, incorporating these components of immunity, recapitulates both the current severity of SARS-CoV-2 infection and the benign nature of HCoVs, suggesting that once the endemic phase is reached and primary exposure is in childhood, SARS-CoV-2 may be no more virulent than the common cold. We predict a different outcome for an emergent coronavirus that causes severe disease in children. These results reinforce the importance of behavioral containment during pandemic vaccine rollout, while prompting us to evaluate scenarios for continuing vaccination in the endemic phase.

The duration of travel impacts the spatial dynamics of infectious diseases.

Humans can impact the spatial transmission dynamics of infectious diseases by introducing pathogens into susceptible environments. The rate at which this occurs depends in part on human-mobility patterns. Increasingly, mobile-phone usage data are used to quantify human mobility and investigate the impact on disease dynamics. Although the number of trips between locations and the duration of those trips could both affect infectious-disease dynamics, there has been limited work to quantify and model the duration of travel in the context of disease transmission. Using mobility data inferred from mobile-phone calling records in Namibia, we calculated both the number of trips between districts and the duration of these trips from 2010 to 2014. We fit hierarchical Bayesian models to these data to describe both the mean trip number and duration. Results indicate that trip duration is positively related to trip distance, but negatively related to the destination population density. The highest volume of trips and shortest trip durations were among high-density districts, whereas trips among low-density districts had lower volume with longer duration. We also analyzed the impact of including trip duration in spatial-transmission models for a range of pathogens and introduction locations. We found that inclusion of trip duration generally delays the rate of introduction, regardless of pathogen, and that the variance and uncertainty around spatial spread increases proportionally with pathogen-generation time. These results enhance our understanding of disease-dispersal dynamics driven by human mobility, which has potential to elucidate optimal spatial and temporal scales for epidemic interventions.

Peste des petits ruminants Virus Transmission Scaling and Husbandry Practices That Contribute to Increased Transmission Risk: An Investigation among Sheep, Goats, and Cattle in Northern Tanzania.

Peste des petits ruminants virus (PPRV) causes an infectious disease of high morbidity and mortality among sheep and goats which impacts millions of livestock keepers globally. PPRV transmission risk varies by production system, but a deeper understanding of how transmission scales in these systems and which husbandry practices impact risk is needed. To investigate transmission scaling and husbandry practice-associated risk, this study combined 395 household questionnaires with over 7115 cross-sectional serosurvey samples collected in Tanzania among agropastoral and pastoral households managing sheep, goats, or cattle (most managed all three, n = 284, 71.9%). Although self-reported compound-level herd size was significantly larger in pastoral than agropastoral households, the data show no evidence that household herd force of infection (FOI, per capita infection rate of susceptible hosts) increased with herd size. Seroprevalence and FOI patterns observed at the sub-village level showed significant spatial variation in FOI. Univariate analyses showed that household herd FOI was significantly higher when households reported seasonal grazing camp attendance, cattle or goat introduction to the compound, death, sale, or giving away of animals in the past 12 months, when cattle were grazed separately from sheep and goats, and when the household also managed dogs or donkeys. Multivariable analyses revealed that species, production system type, and goat or sheep introduction or seasonal grazing camp attendance, cattle or goat death or sales, or goats given away in the past 12 months significantly increased odds of seroconversion, whereas managing pigs or cattle attending seasonal grazing camps had significantly lower odds of seroconversion. Further research should investigate specific husbandry practices across production systems in other countries and in systems that include additional atypical host species to broaden understanding of PPRV transmission.