Publications
91 results found
Hogan A, Winskill P, Watson O, et al., 2020, Report 33: Modelling the allocation and impact of a COVID-19 vaccine
Several SARS-CoV-2 vaccine candidates are now in late-stage trials, with efficacy and safety results expected by the end of 2020. Even under optimistic scenarios for manufacture and delivery, the doses available in 2021 are likely to be limited. Here we identify optimal vaccine allocation strategies within and between countries to maximise health (avert deaths) under constraints on dose supply. We extended an existing mathematical model of SARS-CoV-2 transmission across different country settings to model the public health impact of potential vaccines, using a range of target product profiles developed by the World Health Organization. We show that as supply increases, vaccines that reduce or block infection – and thus transmission – in addition to preventing disease have a greater impact than those that prevent disease alone, due to the indirect protection provided to high-risk groups. We further demonstrate that the health impact of vaccination will depend on the cumulative infection incidence in the population when vaccination begins, the duration of any naturally acquired immunity, the likely trajectory of the epidemic in 2021 and the level of healthcare available to effectively treat those with disease. Within a country, we find that for a limited supply (doses for <20% of the population) the optimal strategy is to target the elderly and other high-risk groups. However, if a larger supply is available, the optimal strategy switches to targeting key transmitters (i.e. the working age population and potentially children) to indirectly protect the elderly and vulnerable. Given the likely global dose supply in 2021 (2 billion doses with a two-dose vaccine), we find that a strategy in which doses are allocated to countries in proportion to their population size is close to optimal in averting deaths. Such a strategy also aligns with the ethical principles agreed in pandemic preparedness planning.
Monod M, Blenkinsop A, Xi X, et al., 2020, Report 32: Targeting interventions to age groups that sustain COVID-19 transmission in the United States, Pages: 1-32
Following inial declines, in mid 2020, a resurgence in transmission of novel coronavirus disease (COVID-19) has occurred in the United States and parts of Europe. Despite the wide implementaon of non-pharmaceucal inter-venons, it is sll not known how they are impacted by changing contact paerns, age and other demographics. As COVID-19 disease control becomes more localised, understanding the age demographics driving transmission and how these impact the loosening of intervenons such as school reopening is crucial. Considering dynamics for the United States, we analyse aggregated, age-specific mobility trends from more than 10 million individuals and link these mechaniscally to age-specific COVID-19 mortality data. In contrast to previous approaches, we link mobility to mortality via age specific contact paerns and use this rich relaonship to reconstruct accurate trans-mission dynamics. Contrary to anecdotal evidence, we find lile support for age-shis in contact and transmission dynamics over me. We esmate that, unl August, 63.4% [60.9%-65.5%] of SARS-CoV-2 infecons in the United States originated from adults aged 20-49, while 1.2% [0.8%-1.8%] originated from children aged 0-9. In areas with connued, community-wide transmission, our transmission model predicts that re-opening kindergartens and el-ementary schools could facilitate spread and lead to considerable excess COVID-19 aributable deaths over a 90-day period. These findings indicate that targeng intervenons to adults aged 20-49 are an important con-sideraon in halng resurgent epidemics, and prevenng COVID-19-aributable deaths when kindergartens and elementary schools reopen.
van Elsland S, Watson O, Alhaffar M, et al., 2020, Report 31: Estimating the burden of COVID-19 in Damascus, Syria: an analysis of novel data sources to infer mortality under-ascertainment
The COVID-19 pandemic has resulted in substantial mortality worldwide. However, to date, countries in the Middle East and Africa have reported substantially lower mortality rates than in Europe and the Americas. One hypothesis is that these countries have been ‘spared’, but another is that deaths have been under-ascertained (deaths that have been unreported due to any number of reasons, for instance due to limited testing capacity). However, the scale of under-ascertainment is difficult to assess with currently available data. In this analysis, we estimate the potential under-ascertainment of COVID-19 mortality in Damascus, Syria, where all-cause mortality data has been reported between 25th July and 1st August. We fit a mathematical model of COVID-19 transmission to reported COVID-19 deaths in Damascus since the beginning of the pandemic and compare the model-predicted deaths to reported excess deaths. Exploring a range of different assumptions about under-ascertainment, we estimate that only 1.25% of deaths (sensitivity range 1% - 3%) due to COVID-19 are reported in Damascus. Accounting for under-ascertainment also corroborates local reports of exceeded hospital bed capacity. To validate the epidemic dynamics inferred, we leverage community-uploaded obituary certificates as an alternative data source, which confirms extensive mortality under-ascertainment in Damascus between July and August. This level of under-ascertainment suggests that Damascus is at a much later stage in its epidemic than suggested by surveillance reports, which have repo. We estimate that 4,340 (95% CI: 3,250 - 5,540) deaths due to COVID-19 in Damascus may have been missed as of 2nd September 2020. Given that Damascus is likely to have the most robust surveillance in Syria, these findings suggest that other regions of the country could have experienced similar or worse mortality rates due to COVID-19.
Watson O, Okell L, Hellewell J, et al., 2020, Evaluating the performance of malaria genetics for inferring changes in transmission intensity using transmission modelling, Molecular Biology and Evolution, Vol: 38, Pages: 274-289, ISSN: 0737-4038
Substantial progress has been made globally to control malaria, however there is a growing need for innovative new tools to ensure continued progress. One approach is to harness genetic sequencing and accompanying methodological approaches as have been used in the control of other infectious diseases. However, to utilise these methodologies for malaria we first need to extend the methods to capture the complex interactions between parasites, human and vector hosts, and environment, which all impact the level of genetic diversity and relatedness of malaria parasites. We develop an individual-based transmission model to simulate malaria parasite genetics parameterised using estimated relationships between complexity of infection and age from 5 regions in Uganda and Kenya. We predict that cotransmission and superinfection contribute equally to within-host parasite genetic diversity at 11.5% PCR prevalence, above which superinfections dominate. Finally, we characterise the predictive power of six metrics of parasite genetics for detecting changes in transmission intensity, before grouping them in an ensemble statistical model. The model predicted malaria prevalence with a mean absolute error of 0.055. Different assumptions about the availability of sample metadata were considered, with the most accurate predictions of malaria prevalence made when the clinical status and age of sampled individuals is known. Parasite genetics may provide a novel surveillance tool for estimating the prevalence of malaria in areas in which prevalence surveys are not feasible. However, the findings presented here reinforce the need for patient metadata to be recorded and made available within all future attempts to use parasite genetics for surveillance.
Hogan A, Jewell B, Sherrard-Smith E, et al., 2020, Potential impact of the COVID-19 pandemic on HIV, TB and malaria in low- and middle-income countries: a modelling study, The Lancet Global Health, Vol: 8, Pages: e1132-e1141, ISSN: 2214-109X
Background: COVID-19 has the potential to cause substantial disruptions to health services, including by cases overburdening the health system or response measures limiting usual programmatic activities. We aimed to quantify the extent to which disruptions in services for human immunodeficiency virus (HIV), tuberculosis (TB) and malaria in low- and middle-income countries with high burdens of those disease could lead to additional loss of life. Methods: We constructed plausible scenarios for the disruptions that could be incurred during the COVID-19 pandemic and used established transmission models for each disease to estimate the additional impact on health that could be caused in selected settings.Findings: In high burden settings, HIV-, TB- and malaria-related deaths over five years may increase by up to 10%, 20% and 36%, respectively, compared to if there were no COVID-19 pandemic. We estimate the greatest impact on HIV to be from interruption to antiretroviral therapy, which may occur during a period of high health system demand. For TB, we estimate the greatest impact is from reductions in timely diagnosis and treatment of new cases, which may result from any prolonged period of COVID-19 suppression interventions. We estimate that the greatest impact on malaria burden could come from interruption of planned net campaigns. These disruptions could lead to loss of life-years over five years that is of the same order of magnitude as the direct impact from COVID-19 in places with a high burden of malaria and large HIV/TB epidemics.Interpretation: Maintaining the most critical prevention activities and healthcare services for HIV, TB and malaria could significantly reduce the overall impact of the COVID-19 pandemic.Funding: Bill & Melinda Gates Foundation, The Wellcome Trust, DFID, MRC
Lavezzo E, Franchin E, Ciavarella C, et al., 2020, Suppression of a SARS-CoV-2 outbreak in the Italian municipality of Vo', Nature, Vol: 584, Pages: 425-429, ISSN: 0028-0836
On the 21st of February 2020 a resident of the municipality of Vo', a small town near Padua, died of pneumonia due to SARS-CoV-2 infection1. This was the first COVID-19 death detected in Italy since the emergence of SARS-CoV-2 in the Chinese city of Wuhan, Hubei province2. In response, the regional authorities imposed the lockdown of the whole municipality for 14 days3. We collected information on the demography, clinical presentation, hospitalization, contact network and presence of SARS-CoV-2 infection in nasopharyngeal swabs for 85.9% and 71.5% of the population of Vo' at two consecutive time points. On the first survey, which was conducted around the time the town lockdown started, we found a prevalence of infection of 2.6% (95% confidence interval (CI) 2.1-3.3%). On the second survey, which was conducted at the end of the lockdown, we found a prevalence of 1.2% (95% Confidence Interval (CI) 0.8-1.8%). Notably, 42.5% (95% CI 31.5-54.6%) of the confirmed SARS-CoV-2 infections detected across the two surveys were asymptomatic (i.e. did not have symptoms at the time of swab testing and did not develop symptoms afterwards). The mean serial interval was 7.2 days (95% CI 5.9-9.6). We found no statistically significant difference in the viral load of symptomatic versus asymptomatic infections (p-values 0.62 and 0.74 for E and RdRp genes, respectively, Exact Wilcoxon-Mann-Whitney test). This study sheds new light on the frequency of asymptomatic SARS-CoV-2 infection, their infectivity (as measured by the viral load) and provides new insights into its transmission dynamics and the efficacy of the implemented control measures.
Flaxman S, Mishra S, Gandy A, et al., 2020, Estimating the effects of non-pharmaceutical interventions on COVID-19 in Europe, Nature, Vol: 584, Pages: 257-261, ISSN: 0028-0836
Following the emergence of a novel coronavirus1 (SARS-CoV-2) and its spread outside of China, Europe has experienced large epidemics. In response, many European countries have implemented unprecedented non-pharmaceutical interventions such as closure of schools and national lockdowns. We study the impact of major interventions across 11 European countries for the period from the start of COVID-19 until the 4th of May 2020 when lockdowns started to be lifted. Our model calculates backwards from observed deaths to estimate transmission that occurred several weeks prior, allowing for the time lag between infection and death. We use partial pooling of information between countries with both individual and shared effects on the reproduction number. Pooling allows more information to be used, helps overcome data idiosyncrasies, and enables more timely estimates. Our model relies on fixed estimates of some epidemiological parameters such as the infection fatality rate, does not include importation or subnational variation and assumes that changes in the reproduction number are an immediate response to interventions rather than gradual changes in behavior. Amidst the ongoing pandemic, we rely on death data that is incomplete, with systematic biases in reporting, and subject to future consolidation. We estimate that, for all the countries we consider, current interventions have been sufficient to drive the reproduction number Rt below 1 (probability Rt< 1.0 is 99.9%) and achieve epidemic control. We estimate that, across all 11 countries, between 12 and 15 million individuals have been infected with SARS-CoV-2 up to 4th May, representing between 3.2% and 4.0% of the population. Our results show that major non-pharmaceutical interventions and lockdown in particular have had a large effect on reducing transmission. Continued intervention should be considered to keep transmission of SARS-CoV-2 under control.
Sherrard-Smith E, Hogan AB, Hamlet A, et al., 2020, The potential public health consequences of COVID-19 on malaria in Africa., Nature Medicine, Vol: 26, Pages: 1411-1416, ISSN: 1078-8956
The burden of malaria is heavily concentrated in sub-Saharan Africa (SSA) where cases and deaths associated with COVID-19 are rising1. In response, countries are implementing societal measures aimed at curtailing transmission of SARS-CoV-22,3. Despite these measures, the COVID-19 epidemic could still result in millions of deaths as local health facilities become overwhelmed4. Advances in malaria control this century have been largely due to distribution of long-lasting insecticidal nets (LLINs)5, with many SSA countries having planned campaigns for 2020. In the present study, we use COVID-19 and malaria transmission models to estimate the impact of disruption of malaria prevention activities and other core health services under four different COVID-19 epidemic scenarios. If activities are halted, the malaria burden in 2020 could be more than double that of 2019. In Nigeria alone, reducing case management for 6 months and delaying LLIN campaigns could result in 81,000 (44,000-119,000) additional deaths. Mitigating these negative impacts is achievable, and LLIN distributions in particular should be prioritized alongside access to antimalarial treatments to prevent substantial malaria epidemics.
Fu H, Xi X, Wang H, et al., 2020, Report 30: The COVID-19 epidemic trends and control measures in mainland China
Okell LC, Verity R, Watson OJ, et al., 2020, Have deaths from COVID-19 in Europe plateaued due to herd immunity?, LANCET, Vol: 395, Pages: E110-E111, ISSN: 0140-6736
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Walker PGT, Whittaker C, Watson OJ, et al., 2020, The impact of COVID-19 and strategies for mitigation and suppression in low- and middle-income countries, Science, Vol: 369, Pages: 413-422, ISSN: 0036-8075
The ongoing COVID-19 pandemic poses a severe threat to public health worldwide. We combine data on demography, contact patterns, disease severity, and health care capacity and quality to understand its impact and inform strategies for its control. Younger populations in lower income countries may reduce overall risk but limited health system capacity coupled with closer inter-generational contact largely negates this benefit. Mitigation strategies that slow but do not interrupt transmission will still lead to COVID-19 epidemics rapidly overwhelming health systems, with substantial excess deaths in lower income countries due to the poorer health care available. Of countries that have undertaken suppression to date, lower income countries have acted earlier. However, this will need to be maintained or triggered more frequently in these settings to keep below available health capacity, with associated detrimental consequences for the wider health, well-being and economies of these countries.
Nouvellet P, Bhatia S, Cori A, et al., 2020, Report 26: Reduction in mobility and COVID-19 transmission
In response to the COVID-19 pandemic, countries have sought to control transmission of SARS-CoV-2by restricting population movement through social distancing interventions, reducing the number ofcontacts.Mobility data represent an important proxy measure of social distancing. Here, we develop aframework to infer the relationship between mobility and the key measure of population-level diseasetransmission, the reproduction number (R). The framework is applied to 53 countries with sustainedSARS-CoV-2 transmission based on two distinct country-specific automated measures of humanmobility, Apple and Google mobility data.For both datasets, the relationship between mobility and transmission was consistent within andacross countries and explained more than 85% of the variance in the observed variation intransmissibility. We quantified country-specific mobility thresholds defined as the reduction inmobility necessary to expect a decline in new infections (R<1).While social contacts were sufficiently reduced in France, Spain and the United Kingdom to controlCOVID-19 as of the 10th of May, we find that enhanced control measures are still warranted for themajority of countries. We found encouraging early evidence of some decoupling of transmission andmobility in 10 countries, a key indicator of successful easing of social-distancing restrictions.Easing social-distancing restrictions should be considered very carefully, as small increases in contactrates are likely to risk resurgence even where COVID-19 is apparently under control. Overall, strongpopulation-wide social-distancing measures are effective to control COVID-19; however gradualeasing of restrictions must be accompanied by alternative interventions, such as efficient contacttracing, to ensure control.
Verity R, Okell LC, Dorigatti I, et al., 2020, Estimates of the severity of coronavirus disease 2019: a model-based analysis., Lancet Infectious Diseases, Vol: 20, Pages: 669-677, ISSN: 1473-3099
BACKGROUND: In the face of rapidly changing data, a range of case fatality ratio estimates for coronavirus disease 2019 (COVID-19) have been produced that differ substantially in magnitude. We aimed to provide robust estimates, accounting for censoring and ascertainment biases. METHODS: We collected individual-case data for patients who died from COVID-19 in Hubei, mainland China (reported by national and provincial health commissions to Feb 8, 2020), and for cases outside of mainland China (from government or ministry of health websites and media reports for 37 countries, as well as Hong Kong and Macau, until Feb 25, 2020). These individual-case data were used to estimate the time between onset of symptoms and outcome (death or discharge from hospital). We next obtained age-stratified estimates of the case fatality ratio by relating the aggregate distribution of cases to the observed cumulative deaths in China, assuming a constant attack rate by age and adjusting for demography and age-based and location-based under-ascertainment. We also estimated the case fatality ratio from individual line-list data on 1334 cases identified outside of mainland China. Using data on the prevalence of PCR-confirmed cases in international residents repatriated from China, we obtained age-stratified estimates of the infection fatality ratio. Furthermore, data on age-stratified severity in a subset of 3665 cases from China were used to estimate the proportion of infected individuals who are likely to require hospitalisation. FINDINGS: Using data on 24 deaths that occurred in mainland China and 165 recoveries outside of China, we estimated the mean duration from onset of symptoms to death to be 17·8 days (95% credible interval [CrI] 16·9-19·2) and to hospital discharge to be 24·7 days (22·9-28·1). In all laboratory confirmed and clinically diagnosed cases from mainland China (n=70 117), we estimated a crude case fatality ratio (adjusted for cen
Deutsch-Feldman M, Brazeau NF, Parr JB, et al., 2020, Spatial and epidemiological drivers of<i>Plasmodium falciparum</i>malaria among adults in the Democratic Republic of the Congo, BMJ GLOBAL HEALTH, Vol: 5, ISSN: 2059-7908
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Dighe A, Cattarino L, Cuomo-Dannenburg G, et al., 2020, Report 25: Response to COVID-19 in South Korea and implications for lifting stringent interventions, 25
While South Korea experienced a sharp growth in COVID-19 cases early in the global pandemic, it has since rapidly reduced rates of infection and now maintains low numbers of daily new cases. Despite using less stringent “lockdown” measures than other affected countries, strong social distancing measures have been advised in high incidence areas and a 38% national decrease in movement occurred voluntarily between February 24th - March 1st. Suspected and confirmed cases were isolated quickly even during the rapid expansion of the epidemic and identification of the Shincheonji cluster. South Korea swiftly scaled up testing capacity and was able to maintain case-based interventions throughout. However, individual case-based contact tracing, not associated with a specific cluster, was a relatively minor aspect of their control program, with cluster investigations accounting for a far higher proportion of cases: the underlying epidemic was driven by a series of linked clusters, with 48% of all cases in the Shincheonji cluster and 20% in other clusters. Case-based contacts currently account for only 11% of total cases. The high volume of testing and low number of deaths suggests that South Korea experienced a small epidemic of infections relative to other countries. Therefore, caution is needed in attempting to duplicate the South Korean response in settings with larger more generalized epidemics. Finding, testing and isolating cases that are linked to clusters may be more difficult in such settings.
Jeffrey B, Walters C, Ainslie K, et al., 2020, Report 24: Mobility data from mobile phones suggests that initial compliance with COVID-19 social distancing interventions was high and geographically consistent across the UK, 24
Since early March 2020, the COVID-19 epidemic across the United Kingdom has led to a range of socialdistancing policies, which have resulted in reduced mobility across different regions. Crowd level dataon mobile phone usage can be used as a proxy for actual population mobility patterns and provide away of quantifying the impact of social distancing measures on changes in mobility. Here, we use twomobile phone-based datasets (anonymised and aggregated crowd level data from O2 and from theFacebook app on mobile phones) to assess changes in average mobility, both overall and broken downinto high and low population density areas, and changes in the distribution of journey lengths. Weshow that there was a substantial overall reduction in mobility with the most rapid decline on the 24thMarch 2020, the day after the Prime Minister’s announcement of an enforced lockdown. Thereduction in mobility was highly synchronized across the UK. Although mobility has remained low since26th March 2020, we detect a gradual increase since that time. We also show that the two differentdatasets produce similar trends, albeit with some location-specific differences. We see slightly largerreductions in average mobility in high-density areas than in low-density areas, with greater variationin mobility in the high-density areas: some high-density areas eliminated almost all mobility. We areonly able to observe populations living in locations where sufficient number of people use Facebookor a device connected to the relevant provider’s network such that no individual is identifiable. Theseanalyses form a baseline with which to monitor changes in behaviour in the UK as social distancing iseased.
Mellan T, Hoeltgebaum H, Mishra S, et al., 2020, Report 21: Estimating COVID-19 cases and reproduction number in Brazil
Brazil is an epicentre for COVID-19 in Latin America. In this report we describe the Brazilian epidemicusing three epidemiological measures: the number of infections, the number of deaths and the reproduction number. Our modelling framework requires sufficient death data to estimate trends, and wetherefore limit our analysis to 16 states that have experienced a total of more than fifty deaths. Thedistribution of deaths among states is highly heterogeneous, with 5 states—São Paulo, Rio de Janeiro,Ceará, Pernambuco and Amazonas—accounting for 81% of deaths reported to date. In these states, weestimate that the percentage of people that have been infected with SARS-CoV-2 ranges from 3.3% (95%CI: 2.8%-3.7%) in São Paulo to 10.6% (95% CI: 8.8%-12.1%) in Amazonas. The reproduction number (ameasure of transmission intensity) at the start of the epidemic meant that an infected individual wouldinfect three or four others on average. Following non-pharmaceutical interventions such as school closures and decreases in population mobility, we show that the reproduction number has dropped substantially in each state. However, for all 16 states we study, we estimate with high confidence that thereproduction number remains above 1. A reproduction number above 1 means that the epidemic isnot yet controlled and will continue to grow. These trends are in stark contrast to other major COVID19 epidemics in Europe and Asia where enforced lockdowns have successfully driven the reproductionnumber below 1. While the Brazilian epidemic is still relatively nascent on a national scale, our resultssuggest that further action is needed to limit spread and prevent health system overload.
Vollmer M, Mishra S, Unwin H, et al., 2020, Report 20: A sub-national analysis of the rate of transmission of Covid-19 in Italy
Italy was the first European country to experience sustained local transmission of COVID-19. As of 1st May 2020, the Italian health authorities reported 28; 238 deaths nationally. To control the epidemic, the Italian government implemented a suite of non-pharmaceutical interventions (NPIs), including school and university closures, social distancing and full lockdown involving banning of public gatherings and non essential movement. In this report, we model the effect of NPIs on transmission using data on average mobility. We estimate that the average reproduction number (a measure of transmission intensity) is currently below one for all Italian regions, and significantly so for the majority of the regions. Despite the large number of deaths, the proportion of population that has been infected by SARS-CoV-2 (the attack rate) is far from the herd immunity threshold in all Italian regions, with the highest attack rate observed in Lombardy (13.18% [10.66%-16.70%]). Italy is set to relax the currently implemented NPIs from 4th May 2020. Given the control achieved by NPIs, we consider three scenarios for the next 8 weeks: a scenario in which mobility remains the same as during the lockdown, a scenario in which mobility returns to pre-lockdown levels by 20%, and a scenario in which mobility returns to pre-lockdown levels by 40%. The scenarios explored assume that mobility is scaled evenly across all dimensions, that behaviour stays the same as before NPIs were implemented, that no pharmaceutical interventions are introduced, and it does not include transmission reduction from contact tracing, testing and the isolation of confirmed or suspected cases. We find that, in the absence of additional interventions, even a 20% return to pre-lockdown mobility could lead to a resurgence in the number of deaths far greater than experienced in the current wave in several regions. Future increases in the number of deaths will lag behind the increase in transmission intensity and so a
Sherrard-Smith E, Hogan A, Hamlet A, et al., 2020, Report 18: The potential public health impact of COVID-19 on malaria in Africa.
The COVID-19 pandemic is likely to severely interrupt health systems in Sub-Saharan Africa (SSA) over the coming weeks and months. Approximately 90% of malaria deaths occur in this region of the world, with an estimated 380,000 deaths from malaria in 2018. Much of the gain made in malaria control over the last decade has been due to the distribution of long-lasting insecticide treated nets (LLINs). Many SSA countries planned to distribute these in 2020. We used COVID-19 and malaria transmission models to understand the likely impact that disruption to these distributions, alongside other core health services, could have on the malaria burden. Results indicate that if all malaria-control activities are highly disrupted then the malaria burden in 2020 could more than double that in the previous year, resulting in large malaria epidemics across the region. These will depend on the course of the COVID-19 epidemic and how it interrupts local health system. Our results also demonstrate that it is essential to prioritise the LLIN distributions either before or as soon as possible into local COVID-19 epidemics to mitigate this risk. Additional planning to ensure other malaria prevention activities are continued where possible, alongside planning to ensure basic access to antimalarial treatment, will further minimise the risk of substantial additional malaria mortality.
Verity R, Aydemir O, Brazeau NF, et al., 2020, The impact of antimalarial resistance on the genetic structure of Plasmodium falciparum in the DRC., Nature Communications, Vol: 11, Pages: 1-10, ISSN: 2041-1723
The Democratic Republic of the Congo (DRC) harbors 11% of global malaria cases, yet little is known about the spatial and genetic structure of the parasite population in that country. We sequence 2537 Plasmodium falciparum infections, including a nationally representative population sample from DRC and samples from surrounding countries, using molecular inversion probes - a high-throughput genotyping tool. We identify an east-west divide in haplotypes known to confer resistance to chloroquine and sulfadoxine-pyrimethamine. Furthermore, we identify highly related parasites over large geographic distances, indicative of gene flow and migration. Our results are consistent with a background of isolation by distance combined with the effects of selection for antimalarial drug resistance. This study provides a high-resolution view of parasite genetic structure across a large country in Africa and provides a baseline to study how implementation programs may impact parasite populations.
Ainslie KEC, Walters CE, Fu H, et al., 2020, Evidence of initial success for China exiting COVID-19 social distancing policy after achieving containment [version 1; peer review: 2 approved], Wellcome Open Res, Vol: 5, ISSN: 2398-502X
Background: The COVID-19 epidemic was declared a Global Pandemic by WHO on 11 March 2020. By 24 March 2020, over 440,000 cases and almost 20,000 deaths had been reported worldwide. In response to the fast-growing epidemic, which began in the Chinese city of Wuhan, Hubei, China imposed strict social distancing in Wuhan on 23 January 2020 followed closely by similar measures in other provinces. These interventions have impacted economic productivity in China, and the ability of the Chinese economy to resume without restarting the epidemic was not clear. Methods: Using daily reported cases from mainland China and Hong Kong SAR, we estimated transmissibility over time and compared it to daily within-city movement, as a proxy for economic activity. Results: Initially, within-city movement and transmission were very strongly correlated in the five mainland provinces most affected by the epidemic and Beijing. However, that correlation decreased rapidly after the initial sharp fall in transmissibility. In general, towards the end of the study period, the correlation was no longer apparent, despite substantial increases in within-city movement. A similar analysis for Hong Kong shows that intermediate levels of local activity were maintained while avoiding a large outbreak. At the very end of the study period, when China began to experience the re-introduction of a small number of cases from Europe and the United States, there is an apparent up-tick in transmission. Conclusions: Although these results do not preclude future substantial increases in incidence, they suggest that after very intense social distancing (which resulted in containment), China successfully exited its lockdown to some degree. Elsewhere, movement data are being used as proxies for economic activity to assess the impact of interventions. The results presented here illustrate how the eventual decorrelation between transmission and movement is likely a key feature of successful COVID-19 exit strategies.
Grassly N, Pons Salort M, Parker E, et al., 2020, Report 16: Role of testing in COVID-19 control
The World Health Organization has called for increased molecular testing in response to the COVID-19 pandemic, but different countries have taken very different approaches. We used a simple mathematical model to investigate the potential effectiveness of alternative testing strategies for COVID-19 control. Weekly screening of healthcare workers (HCWs) and other at-risk groups using PCR or point-of-care tests for infection irrespective of symptoms is estimated to reduce their contribution to transmission by 25-33%, on top of reductions achieved by self-isolation following symptoms. Widespread PCR testing in the general population is unlikely to limit transmission more than contact-tracing and quarantine based on symptoms alone, but could allow earlier release of contacts from quarantine. Immunity passports based on tests for antibody or infection could support return to work but face significant technical, legal and ethical challenges. Testing is essential for pandemic surveillance but its direct contribution to the prevention of transmission is likely to be limited to patients, HCWs and other high-risk groups.
Ainslie K, Walters C, Fu H, et al., 2020, Report 11: Evidence of initial success for China exiting COVID-19 social distancing policy after achieving containment
The COVID-19 epidemic was declared a Global Pandemic by WHO on 11 March 2020. As of 20 March 2020, over 254,000 cases and 10,000 deaths had been reported worldwide. The outbreak began in the Chinese city of Wuhan in December 2019. In response to the fast-growing epidemic, China imposed strict social distancing in Wuhan on 23 January 2020 followed closely by similar measures in other provinces. At the peak of the outbreak in China (early February), there were between 2,000 and 4,000 new confirmed cases per day. For the first time since the outbreak began there have been no new confirmed cases caused by local transmission in China reported for five consecutive days up to 23 March 2020. This is an indication that the social distancing measures enacted in China have led to control of COVID-19 in China. These interventions have also impacted economic productivity in China, and the ability of the Chinese economy to resume without restarting the epidemic is not yet clear. Here, we estimate transmissibility from reported cases and compare those estimates with daily data on within-city movement, as a proxy for economic activity. Initially, within-city movement and transmission were very strongly correlated in the 5 provinces most affected by the epidemic and Beijing. However, that correlation is no longer apparent even though within-city movement has started to increase. A similar analysis for Hong Kong shows that intermediate levels of local activity can be maintained while avoiding a large outbreak. These results do not preclude future epidemics in China, nor do they allow us to estimate the maximum proportion of previous within-city activity that will be recovered in the medium term. However, they do suggest that after very intense social distancing which resulted in containment, China has successfully exited their stringent social distancing policy to some degree. Globally, China is at a more advanced stage of the pandemic. Policies implemented to reduce the spread of CO
Ferguson N, Laydon D, Nedjati Gilani G, et al., 2020, Report 9: Impact of non-pharmaceutical interventions (NPIs) to reduce COVID19 mortality and healthcare demand
The global impact of COVID-19 has been profound, and the public health threat it represents is the most serious seen in a respiratory virus since the 1918 H1N1 influenza pandemic. Here we present the results of epidemiological modelling which has informed policymaking in the UK and other countries in recent weeks. In the absence of a COVID-19 vaccine, we assess the potential role of a number of public health measures – so-called non-pharmaceutical interventions (NPIs) – aimed at reducing contact rates in the population and thereby reducing transmission of the virus. In the results presented here, we apply a previously published microsimulation model to two countries: the UK (Great Britain specifically) and the US. We conclude that the effectiveness of any one intervention in isolation is likely to be limited, requiring multiple interventions to be combined to have a substantial impact on transmission. Two fundamental strategies are possible: (a) mitigation, which focuses on slowing but not necessarily stopping epidemic spread – reducing peak healthcare demand while protecting those most at risk of severe disease from infection, and (b) suppression, which aims to reverse epidemic growth, reducing case numbers to low levels and maintaining that situation indefinitely. Each policy has major challenges. We find that that optimal mitigation policies (combining home isolation of suspect cases, home quarantine of those living in the same household as suspect cases, and social distancing of the elderly and others at most risk of severe disease) might reduce peak healthcare demand by 2/3 and deaths by half. However, the resulting mitigated epidemic would still likely result in hundreds of thousands of deaths and health systems (most notably intensive care units) being overwhelmed many times over. For countries able to achieve it, this leaves suppression as the preferred policy option. We show that in the UK and US context, suppression will minimally requi
Gaythorpe K, Imai N, Cuomo-Dannenburg G, et al., 2020, Report 8: Symptom progression of COVID-19
The COVID-19 epidemic was declared a Public Health Emergency of International Concern (PHEIC) by WHO on 30th January 2020 [1]. As of 8 March 2020, over 107,000 cases had been reported. Here, we use published and preprint studies of clinical characteristics of cases in mainland China as well as case studies of individuals from Hong Kong, Japan, Singapore and South Korea to examine the proportional occurrence of symptoms and the progression of symptoms through time.We find that in mainland China, where specific symptoms or disease presentation are reported, pneumonia is the most frequently mentioned, see figure 1. We found a more varied spectrum of severity in cases outside mainland China. In Hong Kong, Japan, Singapore and South Korea, fever was the most frequently reported symptom. In this latter group, presentation with pneumonia is not reported as frequently although it is more common in individuals over 60 years old. The average time from reported onset of first symptoms to the occurrence of specific symptoms or disease presentation, such as pneumonia or the use of mechanical ventilation, varied substantially. The average time to presentation with pneumonia is 5.88 days, and may be linked to testing at hospitalisation; fever is often reported at onset (where the mean time to develop fever is 0.77 days).
Jeffrey B, Walters CE, Ainslie KEC, et al., 2020, Anonymised and aggregated crowd level mobility data from mobile phones suggests that initial compliance with COVID-19 social distancing interventions was high and geographically consistent across the UK., Wellcome open research, Vol: 5, ISSN: 2398-502X
<b>Background:</b> Since early March 2020, the COVID-19 epidemic across the United Kingdom has led to a range of social distancing policies, which have resulted in reduced mobility across different regions. Crowd level data on mobile phone usage can be used as a proxy for actual population mobility patterns and provide a way of quantifying the impact of social distancing measures on changes in mobility. <b>Methods:</b> Here, we use two mobile phone-based datasets (anonymised and aggregated crowd level data from O2 and from the Facebook app on mobile phones) to assess changes in average mobility, both overall and broken down into high and low population density areas, and changes in the distribution of journey lengths. <b>Results:</b> We show that there was a substantial overall reduction in mobility, with the most rapid decline on the 24th March 2020, the day after the Prime Minister's announcement of an enforced lockdown. The reduction in mobility was highly synchronized across the UK. Although mobility has remained low since 26th March 2020, we detect a gradual increase since that time. We also show that the two different datasets produce similar trends, albeit with some location-specific differences. We see slightly larger reductions in average mobility in high-density areas than in low-density areas, with greater variation in mobility in the high-density areas: some high-density areas eliminated almost all mobility. <b>Conclusions:</b> These analyses form a baseline from which to observe changes in behaviour in the UK as social distancing is eased and inform policy towards the future control of SARS-CoV-2 in the UK.
Jeffrey B, Walters CE, Ainslie KEC, et al., 2020, Anonymised and aggregated crowd level mobility data from mobile phones suggests that initial compliance with COVID-19 social distancing interventions was high and geographically consistent across the UK., Wellcome Open Res, Vol: 5, ISSN: 2398-502X
Background: Since early March 2020, the COVID-19 epidemic across the United Kingdom has led to a range of social distancing policies, which have resulted in reduced mobility across different regions. Crowd level data on mobile phone usage can be used as a proxy for actual population mobility patterns and provide a way of quantifying the impact of social distancing measures on changes in mobility. Methods: Here, we use two mobile phone-based datasets (anonymised and aggregated crowd level data from O2 and from the Facebook app on mobile phones) to assess changes in average mobility, both overall and broken down into high and low population density areas, and changes in the distribution of journey lengths. Results: We show that there was a substantial overall reduction in mobility, with the most rapid decline on the 24th March 2020, the day after the Prime Minister's announcement of an enforced lockdown. The reduction in mobility was highly synchronized across the UK. Although mobility has remained low since 26th March 2020, we detect a gradual increase since that time. We also show that the two different datasets produce similar trends, albeit with some location-specific differences. We see slightly larger reductions in average mobility in high-density areas than in low-density areas, with greater variation in mobility in the high-density areas: some high-density areas eliminated almost all mobility. Conclusions: These analyses form a baseline from which to observe changes in behaviour in the UK as social distancing is eased and inform policy towards the future control of SARS-CoV-2 in the UK.
Deutsch-Feldman M, Aydemir O, Carrel M, et al., 2019, The changing landscape of <i>Plasmodium falciparum</i> drug resistance in the Democratic Republic of Congo, BMC INFECTIOUS DISEASES, Vol: 19
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Boyce RM, Delamater P, Muhindo R, et al., 2019, Accessible metrics of access: Novel tools to measure immunization coverage in rural sub-Saharan Africa, Gates Open Research, Vol: 3, Pages: 1540-1540
<ns4:p>Immunization rates in most sub-Saharan African countries fall far below stated targets. Measuring access in resource-limited settings, however, is challenging, especially with the data available at the district level, which is the primary administrative division for most immunization programs. Despite calls to improve routine data collection and use, there remains a lack of structured methods and practical tools to target underserved populations. Herein, we describe a prospective study that aims to develop, pilot, and validate a set of user-friendly tools to identify geographic areas with limited access to immunization services and by extension, low immunization coverage. The approach will leverage routinely-collected data from public health facilities combined with novel methods of household mapping to perform spatial analyses using open-access platforms. In addition, we will triangulate the analyses across datasets representing common reasons for care seeking – namely, visits for vaccination, antenatal care, and malaria – to improve the accuracy of our estimates. The ultimate goal of this project is to equip front-line providers and district level program managers with novel tools that facilitate timely and accurate analysis of routinely-collected data to guide immunization efforts.</ns4:p>
Watson OJ, Verity R, Ghani AC, et al., 2019, Impact of seasonal variations in Plasmodium falciparum malaria transmission on the surveillance of pfhrp2 gene deletions, eLife, Vol: 8, ISSN: 2050-084X
Ten countries have reported pfhrp2/pfhrp3 gene deletions since the first observation of pfhrp2-deleted parasites in 2012. In a previous study (Watson et al., 2017) we characterised the drivers selecting for pfhrp2/3 deletions, and mapped the regions in Africa with the greatest selection pressure. In February 2018, the World Health Organization issued guidance on investigating suspected false-negative rapid diagnostic tests (RDTs) due to pfhrp2/3 deletions. However, no guidance is provided regarding the timing of investigations. Failure to consider seasonal variation could cause premature decisions to switch to alternative RDTs. In response, we have extended our methods and predict that the prevalence of false-negative RDTs due to pfhrp2/3 deletions is highest when sampling from younger individuals during the beginning of the rainy season. We conclude by producing a map of the regions impacted by seasonal fluctuations in pfhrp2/3 deletions and a database identifying optimum sampling intervals to support malaria control programmes.
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