For the 2009 influenza A H1N1 pandemic, in most infected people these epidemiological quantities were short with a day or so to infectiousness and a few days of peak infectiousness to others.3 By ...contrast, for COVID-19, the serial interval is estimated at 4·4–7·5 days, which is more similar to SARS.4 First among the important unknowns about COVID-19 is the case fatality rate (CFR), which requires information on the denominator that defines the number infected. ...the effect of seasons on transmission of COVID-19 is unknown;11 however, with an R0 of 2–3, the warm months of summer in the northern hemisphere might not necessarily reduce transmission below the value of unity as they do for influenza A, which typically has an R0 of around 1·1–1·5.12 Closely linked to these factors and their epidemiological determinants is the impact of different mitigation policies on the course of the COVID-19 epidemic. A key issue for epidemiologists is helping policy makers decide the main objectives of mitigation—eg, minimising morbidity and associated mortality, avoiding an epidemic peak that overwhelms health-care services, keeping the effects on the economy within manageable levels, and flattening the epidemic curve to wait for vaccine development and manufacture on scale and antiviral drug therapies. Avoiding large gatherings of people will reduce the number of super-spreading events; however, if prolonged contact is required for transmission, this measure might only reduce a small proportion of transmissions. ...broader-scale social distancing is likely to be needed, as was put in place in China.
Contact tracing is a central public health response to infectious disease outbreaks, especially in the early stages of an outbreak when specific treatments are limited. Importation of novel ...coronavirus (COVID-19) from China and elsewhere into the UK highlights the need to understand the impact of contact tracing as a control measure.
Detailed survey information on social encounters from over 5800 respondents is coupled to predictive models of contact tracing and control. This is used to investigate the likely efficacy of contact tracing and the distribution of secondary cases that may go untraced.
Taking recent estimates for COVID-19 transmission we predict that under effective contact tracing less than 1 in 6 cases will generate any subsequent untraced infections, although this comes at a high logistical burden with an average of 36 individuals traced per case. Changes to the definition of a close contact can reduce this burden, but with increased risk of untraced cases; we find that tracing using a contact definition requiring more than 4 hours of contact is unlikely to control spread.
The current contact tracing strategy within the UK is likely to identify a sufficient proportion of infected individuals such that subsequent spread could be prevented, although the ultimate success will depend on the rapid detection of cases and isolation of contacts. Given the burden of tracing a large number of contacts to find new cases, there is the potential the system could be overwhelmed if imports of infection occur at a rapid rate.
Abstract
Background
The COVID-19 pandemic has disrupted planned annual antibiotic mass drug administration (MDA) activities that have formed the cornerstone of the largely successful global efforts ...to eliminate trachoma as a public health problem.
Methods
Using a mathematical model we investigate the impact of interruption to MDA in trachoma-endemic settings. We evaluate potential measures to mitigate this impact and consider alternative strategies for accelerating progress in those areas where the trachoma elimination targets may not be achievable otherwise.
Results
We demonstrate that for districts that were hyperendemic at baseline, or where the trachoma elimination thresholds have not already been achieved after three rounds of MDA, the interruption to planned MDA could lead to a delay to reaching elimination targets greater than the duration of interruption. We also show that an additional round of MDA in the year following MDA resumption could effectively mitigate this delay. For districts where the probability of elimination under annual MDA was already very low, we demonstrate that more intensive MDA schedules are needed to achieve agreed targets.
Conclusion
Through appropriate use of additional MDA, the impact of COVID-19 in terms of delay to reaching trachoma elimination targets can be effectively mitigated. Additionally, more frequent MDA may accelerate progress towards 2030 goals.
Why some individuals develop AIDS rapidly whereas others remain healthy without treatment for many years remains a central question of HIV research. An evolutionary perspective reveals an apparent ...conflict between two levels of selection on the virus. On the one hand, there is rapid evolution of the virus in the host, and on the other, new observations indicate the existence of virus factors that affect the virulence of infection whose influence persists over years in infected individuals and across transmission events. Here, we review recent evidence that shows that viral genetic factors play a larger role in modulating disease severity than anticipated. We propose conceptual models that reconcile adaptive evolution at both levels of selection. Evolutionary analysis provides new insight into HIV pathogenesis.
In many countries where lockdown measures were relaxed early, such as the USA, parts of Australia, and some countries in western mainland Europe, resurgence of cases has been recorded.2 Informative ...data on epidemics derive from longitudinal (over time) cohort-based (following the same individuals) studies of seroprevalence of past infections and the incidence of new infections, stratified by age, gender, ethnicity, occupation, pre-existing health conditions, spatial home and work or school locations, and clinical outcomes. Uneven quality and slow access to information on COVID-19 spread and impact, collected by different government organisations, such as the Department of Health and Social Care, Public Health England, and NHS Trusts, have been major impediments to epidemiological analysis of the state of the epidemic and predictions of future trends (Anderson RM, Vegvari C, Baggaley RF, Hollingsworth TD, Maddren R, unpublished). The UK Government's advisory group, SAGE, has broadened the information they release to include the effective reproduction number, Rt, which describes the average number of secondary cases generated by primary cases at time t, and the epidemic growth rate, rt, which describes the rate of change in case numbers over a defined time.8,9 The value of rt is easier to estimate using simple statistical methods on changes in incidence over time. ...of importance is the probability distribution of the generation of secondary cases,17–19 which is overdispersed such that most infected individuals transmit none or a few infections, and a few individuals transmit many—the so-called super-spreading events.20 Contact tracing data provide crucial insights on this distribution, which has important consequences for COVID-19 control.21 A schematic representation of uncertainty in determining the magnitude of Rt and the course of the COVID-19 epidemic in the UK is shown in the figure with further information in the appendix.
It is estimated that 190 million individuals are at risk of blindness from trachoma, and that control by mass drug administration (MDA) is reducing this risk in many populations. Programs are ...monitored using prevalence of follicular trachoma disease (TF) in children. However, as programs progress to low prevalence there are challenges interpreting this indirect measure of infection. PCR and sero-surveillance are being considered as complementary tools to monitor low-level transmission, but there are questions on how they can be most effectively used. We use a previously-published, mathematical model to explore the dynamic relationship between TF and PCR throughout a control program and a sero-catalytic model to evaluate the utility of two cross-sectional sero-surveys for estimating sero-conversion rates. The simulations show that whilst PCR is more sensitive than TF at detecting infection, the probability of detecting at least one positive individual declines during an MDA program more quickly for PCR than for TF (for the same sample size). Towards the end of a program there is a moderate chance of a random sample showing both low PCR prevalence and higher TF prevalence, which may contribute to the lack of correlation observed in epidemiological studies. We also show that conducting two cross-sectional sero-surveys 10 years apart can provide more precise and accurate estimation of epidemiological parameters than a single survey, supporting previous findings that whilst serology holds great promise, multiple cross-sections from the same community are needed to generate the most valuable information about transmission. These results highlight that the quantitative dynamics of infection and disease should be included alongside the many logistical and practical factors to be considered in designing a monitoring and evaluation strategy at the operational research level, in order to help subsequently inform data collection for individual country programs. Whilst our simulations provide some insight, they also highlight that some level of longitudinal, individual-level data on reinfection and disease may be needed to monitor elimination progress.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A combination of methods, including mathematical model construction, demographic plus epidemiological data analysis and parameter estimation, are used to examine whether mass drug administration ...(MDA) alone can eliminate the transmission of soil-transmitted helminths (STHs). Numerical analyses suggest that in all but low transmission settings (as defined by the magnitude of the basic reproductive number, R0), the treatment of pre-school-aged children (pre-SAC) and school-aged children (SAC) is unlikely to drive transmission to a level where the parasites cannot persist. High levels of coverage (defined as the fraction of an age group effectively treated) are required in pre-SAC, SAC and adults, if MDA is to drive the parasite below the breakpoint under which transmission is eliminated. Long-term solutions to controlling helminth infections lie in concomitantly improving the quality of the water supply, sanitation and hygiene (WASH). MDA, however, is a very cost-effective tool in long-term control given that most drugs are donated free by the pharmaceutical industry for poor regions of the world. WASH interventions, by lowering the basic reproductive number, can facilitate the ability of MDA to interrupt transmission.
A novel influenza A (H1N1) virus has spread rapidly across the globe. Judging its pandemic potential is difficult with limited data, but nevertheless essential to inform appropriate health responses. ...By analyzing the outbreak in Mexico, early data on international spread, and viral genetic diversity, we make an early assessment of transmissibility and severity. Our estimates suggest that 23,000 (range 6000 to 32,000) individuals had been infected in Mexico by late April, giving an estimated case fatality ratio (CFR) of 0.4% (range: 0.3 to 1.8%) based on confirmed and suspected deaths reported to that time. In a community outbreak in the small community of La Gloria, Veracruz, no deaths were attributed to infection, giving an upper 95% bound on CFR of 0.6%. Thus, although substantial uncertainty remains, clinical severity appears less than that seen in the 1918 influenza pandemic but comparable with that seen in the 1957 pandemic. Clinical attack rates in children in La Gloria were twice that in adults (<15 years of age: 61%; greater-than-or-equal15 years: 29%). Three different epidemiological analyses gave basic reproduction number (R₀) estimates in the range of 1.4 to 1.6, whereas a genetic analysis gave a central estimate of 1.2. This range of values is consistent with 14 to 73 generations of human-to-human transmission having occurred in Mexico to late April. Transmissibility is therefore substantially higher than that of seasonal flu, and comparable with lower estimates of R₀ obtained from previous influenza pandemics.
Vector control is a vital tool utilised by malaria control and elimination programmes worldwide, and as such it is important that we can accurately quantify the expected public health impact of these ...methods. There are very few previous models that consider vector-control-induced changes in the age-structure of the vector population and the resulting impact on transmission. We analytically derive the steady-state solution of a novel age-structured deterministic compartmental model describing the mosquito feeding cycle, with mosquito age represented discretely by parity-the number of cycles (or successful bloodmeals) completed. Our key model output comprises an explicit, analytically tractable solution that can be used to directly quantify key transmission statistics, such as the effective reproductive ratio under control, Rc, and investigate the age-structured impact of vector control. Application of this model reinforces current knowledge that adult-acting interventions, such as indoor residual spraying of insecticides (IRS) or long-lasting insecticidal nets (LLINs), can be highly effective at reducing transmission, due to the dual effects of repelling and killing mosquitoes. We also demonstrate how larval measures can be implemented in addition to adult-acting measures to reduce Rc and mitigate the impact of waning insecticidal efficacy, as well as how mid-ranges of LLIN coverage are likely to experience the largest effect of reduced net integrity on transmission. We conclude that whilst well-maintained adult-acting vector control measures are substantially more effective than larval-based interventions, incorporating larval control in existing LLIN or IRS programmes could substantially reduce transmission and help mitigate any waning effects of adult-acting measures.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The control of neglected tropical diseases (NTDs) has received huge investment in recent years, leading to large reductions in morbidity. In 2012, the World Health Organization set ambitious targets ...for eliminating many of these diseases as a public health problem by 2020, an aspiration that was supported by donations of treatments, intervention materials, and funding committed by a broad partnership of stakeholders in the London Declaration on NTDs. Alongside these efforts, there has been an increasing role for quantitative analysis and modeling to support the achievement of these goals through evaluation of the likely impact of interventions, the factors that could undermine these achievements, and the role of new diagnostics and treatments in reducing transmission. In this special issue, we aim to summarize those insights in an accessible way. This article acts as an introduction to the special issue, outlining key concepts in NTDs and insights from modeling as we approach 2020.
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