60 results found
Walker P, Cairns M, Slater H, et al., Modelling the incremental benefit of introducing malaria screening strategies to antenatal care in Africa, Nature Communications, ISSN: 2041-1723
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, 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
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.
Flaxman S, Mishra S, Gandy A, et al., 2020, Estimating the effects of non-pharmaceutical interventions on COVID-19 in Europe, Nature, 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.
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
Unwin H, Mishra S, Bradley VC, et al., 2020, Report 23: State-level tracking of COVID-19 in the United States
our estimates show that the percentage of individuals that have been infected is 4.1% [3.7%-4.5%], with widevariation between states. For all states, even for the worst affected states, we estimate that less than a quarter of thepopulation has been infected; in New York, for example, we estimate that 16.6% [12.8%-21.6%] of individuals have beeninfected to date. Our attack rates for New York are in line with those from recent serological studies  broadly supportingour choice of infection fatality rate.There is variation in the initial reproduction number, which is likely due to a range of factors; we find a strong associationbetween the initial reproduction number with both population density (measured at the state level) and the chronologicaldate when 10 cumulative deaths occurred (a crude estimate of the date of locally sustained transmission).Our estimates suggest that the epidemic is not under control in much of the US: as of 17 May 2020 the reproductionnumber is above the critical threshold (1.0) in 24 [95% CI: 20-30] states. Higher reproduction numbers are geographicallyclustered in the South and Midwest, where epidemics are still developing, while we estimate lower reproduction numbersin states that have already suffered high COVID-19 mortality (such as the Northeast). These estimates suggest that cautionmust be taken in loosening current restrictions if effective additional measures are not put in place.We predict that increased mobility following relaxation of social distancing will lead to resurgence of transmission, keepingall else constant. We predict that deaths over the next two-month period could exceed current cumulative deathsby greater than two-fold, if the relationship between mobility and transmission remains unchanged. Our results suggestthat factors modulating transmission such as rapid testing, contact tracing and behavioural precautions are crucial to offsetthe rise of transmission associated with loosening of social distancing. Overall, we
Winskill P, Whittaker C, Walker P, et al., 2020, Report 22: Equity in response to the COVID-19 pandemic: an assessment of the direct and indirect impacts on disadvantaged and vulnerable populations in low- and lower middle-income countries, 22
The impact of the COVID-19 pandemic in low-income settings is likely to be more severe due to limited healthcare capacity. Within these settings, however, there exists unfair or avoidable differences in health among different groups in society – health inequities – that mean that some groups are particularly at risk from the negative direct and indirect consequences of COVID-19. The structural determinants of these are often reflected in differences by income strata, with the poorest populations having limited access to preventative measures such as handwashing. Their more fragile income status will also mean that they are likely to be employed in occupations that are not amenable to social-distancing measures, thereby further reducing their ability to protect themselves from infection. Furthermore, these populations may also lack access to timely healthcare on becoming ill. We explore these relationships by using large-scale household surveys to quantify the differences in handwashing access, occupation and hospital access with respect to wealth status in low-income settings. We use a COVID-19 transmission model to demonstrate the impact of these differences. Our results demonstrate clear trends that the probability of death from COVID-19 increases with increasing poverty. On average, we estimate a 32.0% (2.5th-97.5th centile 8.0%-72.5%) increase in the probability of death in the poorest quintile compared to the wealthiest quintile from these three factors alone. We further explore how risk mediators and the indirect impacts of COVID-19 may also hit these same disadvantaged and vulnerable the hardest. We find that larger, inter-generational households that may hamper efforts to protect the elderly if social distancing are associated with lower-income countries and, within LMICs, lower wealth status. Poorer populations are also more susceptible to food security issues - with these populations having the highest levels under-nourishment whilst also being
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
Hogan A, Jewell B, Sherrard-Smith E, et al., 2020, Report 19: The potential impact of the COVID-19 epidemic on HIV, TB and malaria in low- and middle-income countries
COVID-19 has the potential to cause disruptions to health services in different ways; through the health system becoming overwhelmed with COVID-19 patients, through the intervention used to slow transmission of COVID-19 inhibiting access to preventative interventions and services, and through supplies of medicine being interrupted. We aim to quantify the extent to which such disruptions in services for HIV, TB and malaria in high burden low- and middle-income countries could lead to additional loss of life. In high burden settings, HIV, TB and malaria related deaths over 5 years may be increased by up to 10%, 20% and 36%, respectively, compared to if there were no COVID-19 epidemic. We estimate the greatest impact on HIV to be from interruption to ART, which may occur during a period of high or extremely 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 a long period of COVID-19 suppression interventions; for malaria, we estimate that the greatest impact could come from reduced prevention activities including interruption of planned net campaigns, through all phases of the COVID-19 epidemic. In high burden settings, the impact of each type of disruption could be significant and lead to a 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. Maintaining the most critical prevention activities and healthcare services for HIV, TB and malaria could significantly reduce the overall impact of the COVID-19 epidemic.
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.
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.
Slater HC, Foy BD, Kobylinski K, et al., 2020, Ivermectin as a novel complementary malaria control tool to reduce incidence and prevalence: a modelling study, Lancet Infectious Diseases, Vol: 20, Pages: 498-508, ISSN: 1473-3099
BACKGROUND: Ivermectin is a potential new vector control tool to reduce malaria transmission. Mosquitoes feeding on a bloodmeal containing ivermectin have a reduced lifespan, meaning they are less likely to live long enough to complete sporogony and become infectious. We aimed to estimate the effect of ivermectin on malaria transmission in various scenarios of use. METHODS: We validated an existing population-level mathematical model of the effect of ivermectin mass drug administration (MDA) on the mosquito population and malaria transmission against two datasets: clinical data from a cluster- randomised trial done in Burkina Faso in 2015 wherein ivermectin was given to individuals taller than 90 cm and entomological data from a study of mosquito outcomes after ivermectin MDA for onchocerciasis or lymphatic filariasis in Burkina Faso, Senegal, and Liberia between 2008 and 2013. We extended the existing model to include a range of complementary malaria interventions (seasonal malaria chemoprevention and MDA with dihydroartemisinin-piperaquine) and to incorporate new data on higher doses of ivermectin with a longer mosquitocidal effect. We consider two ivermectin regimens: a single dose of 400 μg/kg (1 × 400 μg/kg) and three consecutive daily doses of 300 μg/kg per day (3 × 300 μg/kg). We simulated the effect of these two doses in a range of usage scenarios in different transmission settings (highly seasonal, seasonal, and perennial). We report percentage reductions in clinical incidence and slide prevalence. FINDINGS: We estimate that MDA with ivermectin will reduce prevalence and incidence and is most effective in areas with highly seasonal transmission. In a highly seasonal moderate transmission setting, three rounds of ivermectin only MDA at 3 × 300 μg/kg (rounds spaced 1 month apart) and 70% coverage is predicted to reduce clinical incidence by 71% and prevalence by 34%. We predict that adding ivermectin MDA to seasonal malaria ch
Flaxman S, Mishra S, Gandy A, et al., 2020, Report 13: Estimating the number of infections and the impact of non-pharmaceutical interventions on COVID-19 in 11 European countries
Following the emergence of a novel coronavirus (SARS-CoV-2) and its spread outside of China, Europe is now experiencing large epidemics. In response, many European countries have implemented unprecedented non-pharmaceutical interventions including case isolation, the closure of schools and universities, banning of mass gatherings and/or public events, and most recently, widescale social distancing including local and national lockdowns. In this report, we use a semi-mechanistic Bayesian hierarchical model to attempt to infer the impact of these interventions across 11 European countries. Our methods assume that changes in the reproductive number – a measure of transmission - are an immediate response to these interventions being implemented rather than broader gradual changes in behaviour. Our model estimates these changes by calculating backwards from the deaths observed over time to estimate transmission that occurred several weeks prior, allowing for the time lag between infection and death. One of the key assumptions of the model is that each intervention has the same effect on the reproduction number across countries and over time. This allows us to leverage a greater amount of data across Europe to estimate these effects. It also means that our results are driven strongly by the data from countries with more advanced epidemics, and earlier interventions, such as Italy and Spain. We find that the slowing growth in daily reported deaths in Italy is consistent with a significant impact of interventions implemented several weeks earlier. In Italy, we estimate that the effective reproduction number, Rt, dropped to close to 1 around the time of lockdown (11th March), although with a high level of uncertainty. Overall, we estimate that countries have managed to reduce their reproduction number. Our estimates have wide credible intervals and contain 1 for countries that have implemented all interventions considered in our analysis. This means that the reproducti
Walker P, Whittaker C, Watson O, et al., 2020, Report 12: The global impact of COVID-19 and strategies for mitigation and suppression
The world faces a severe and acute public health emergency due to the ongoing COVID-19 global pandemic. How individual countries respond in the coming weeks will be critical in influencing the trajectory of national epidemics. Here we combine data on age-specific contact patterns and COVID-19 severity to project the health impact of the pandemic in 202 countries. We compare predicted mortality impacts in the absence of interventions or spontaneous social distancing with what might be achieved with policies aimed at mitigating or suppressing transmission. Our estimates of mortality and healthcare demand are based on data from China and high-income countries; differences in underlying health conditions and healthcare system capacity will likely result in different patterns in low income settings. We estimate that in the absence of interventions, COVID-19 would have resulted in 7.0 billion infections and 40 million deaths globally this year. Mitigation strategies focussing on shielding the elderly (60% reduction in social contacts) and slowing but not interrupting transmission (40% reduction in social contacts for wider population) could reduce this burden by half, saving 20 million lives, but we predict that even in this scenario, health systems in all countries will be quickly overwhelmed. This effect is likely to be most severe in lower income settings where capacity is lowest: our mitigated scenarios lead to peak demand for critical care beds in a typical low-income setting outstripping supply by a factor of 25, in contrast to a typical high-income setting where this factor is 7. As a result, we anticipate that the true burden in low income settings pursuing mitigation strategies could be substantially higher than reflected in these estimates. Our analysis therefore suggests that healthcare demand can only be kept within manageable levels through the rapid adoption of public health measures (including testing and isolation of cases and wider social distancing meas
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 . 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).
Kitojo C, Gutman JR, Chacky F, et al., 2019, Estimating malaria burden among pregnant women using data from antenatal care centres in Tanzania: a population-based study, The Lancet Global Health, Vol: 7, Pages: e1695-e1705, ISSN: 2214-109X
BACKGROUND: More timely estimates of malaria prevalence are needed to inform optimal control strategies and measure progress. Since 2014, Tanzania has implemented nationwide malaria screening for all pregnant women within the antenatal care system. We aimed to compare malaria test results during antenatal care to two population-based prevalence surveys in Tanzanian children aged 6-59 months to examine their potential in measuring malaria trends and progress towards elimination. METHODS: Malaria test results from pregnant women screened at their first antenatal care visits at health-care facilities (private and public) in all 184 districts of Tanzania between Jan 1, 2014, and Dec 31, 2017, were collected from the Health Management Information Systems and District Health Information System 2. We excluded facilities with no recorded antenatal care attendees during the time period. We standardised results to account for testing uptake and weighted them by the timing of two population-based surveys of childhood malaria prevalence done in 2015-16 (Demographic and Health Survey) and 2017 (Malaria Indicator Survey). We assessed regional-level correlation using Spearman's coefficient and assessed the consistency of monthly district-level prevalence ranking using Kendall's correlation coefficient. FINDINGS: Correlation between malaria prevalence at antenatal care and among children younger than 5 years was high (r≥0·83 for both surveys), although declines in prevalence at antenatal care were generally smaller than among children. Consistent heterogeneity (p<0·05) in antenatal care prevalence at the district level was evident in all but one region (Kilimanjaro). Data from antenatal care showed declining prevalence in three regions (Arusha, Kilimanjaro, and Manyara) where surveys estimated zero prevalence. INTERPRETATION: Routine antenatal care-based screening can be used to assess heterogeneity in transmission at finer resolution than population-based surve
Mayor A, Menendez C, Walker PGT, 2019, Targeting pregnant women for malaria surveillance, Trends in Parasitology, Vol: 35, Pages: 677-686, ISSN: 0169-4758
Women attending antenatal care (ANC) are a generally healthy, easy-access population, contributing valuable data for infectious disease surveillance at the community level. ANC-based malaria surveillance would provide a routine measure of the malaria burden in pregnancy, which countries lack, whilst potentially improving pregnancy outcomes. It could also offer contemporary information on temporal trends and the geographic distribution of malaria burden as well as intervention coverage in the population to guide resource allocation and to assess progress towards elimination. Here, we review the factors underlying the relationship between Plasmodium falciparum in pregnancy and in the community, and outline strengths and limitations of an ANC-based surveillance in sub-Saharan Africa, its potential role within wider malaria surveillance systems, and subsequent programmatic applications.
Winskill P, Walker PG, Cibulskis RE, et al., 2019, Prioritizing the scale-up of interventions for malaria control and elimination, Malaria Journal, Vol: 18, ISSN: 1475-2875
BackgroundA core set of intervention and treatment options are recommended by the World Health Organization for use against falciparum malaria. These are treatment, long-lasting insecticide-treated bed nets, indoor residual spraying, and chemoprevention options. Both domestic and foreign aid funding for these tools is limited. When faced with budget restrictions, the introduction and scale-up of intervention and treatment options must be prioritized.MethodsEstimates of the cost and impact of different interventions were combined with a mathematical model of malaria transmission to estimate the most cost-effective prioritization of interventions. The incremental cost effectiveness ratio was used to select between scaling coverage of current interventions or the introduction of an additional intervention tool.ResultsPrevention, in the form of vector control, is highly cost effective and scale-up is prioritized in all scenarios. Prevention reduces malaria burden and therefore allows treatment to be implemented in a more cost-effective manner by reducing the strain on the health system. The chemoprevention measures (seasonal malaria chemoprevention and intermittent preventive treatment in infants) are additional tools that, provided sufficient funding, are implemented alongside treatment scale-up. Future tools, such as RTS,S vaccine, have impact in areas of higher transmission but were introduced later than core interventions.ConclusionsIn a programme that is budget restricted, it is essential that investment in available tools be effectively prioritized to maximize impact for a given investment. The cornerstones of malaria control: vector control and treatment, remain vital, but questions of when to scale and when to introduce other interventions must be rigorously assessed. This quantitative analysis considers the scale-up or core interventions to inform decision making in this area.
Winskill P, Walker P, Cibulskis R, et al., 2018, Prioritizing the scale up of interventions for malaria control and elimination, Malaria Journal, ISSN: 1475-2875
Samuels AM, Towett O, Seda B, et al., 2019, DIAGNOSTIC PERFORMANCE OF ULTRA-SENSITIVE RAPID DIAGNOSTIC TESTS FOR MALARIA IN PREGNANT WOMEN ATTENDING ANTENATAL CLINICS IN WESTERN KENYA, 68th Annual Meeting of the American-Society-for-Tropical-Medicine-and-Hygiene (ASTMH), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 276-276, ISSN: 0002-9637
Cuomo-Dannenburg GM, Walker P, Verity R, et al., 2019, IMPLICATION OF SULFADOXINE-PYRIMETHAMINE RESISTANCE-ASSOCIATED MUTATIONS ON THE PROTECTIVE EFFICACY OF SEASONAL MALARIA CHEMOPREVENTION: A PHARMACOKINETIC-PHARMACODYNAMIC ANALYSIS, 68th Annual Meeting of the American-Society-for-Tropical-Medicine-and-Hygiene (ASTMH), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 189-189, ISSN: 0002-9637
Hellewell J, Walker P, Ghani A, et al., 2018, Using ante-natal clinic prevalence data to monitor temporal changes in malaria incidence in a humanitarian setting in the Democratic Republic of Congo, Malaria Journal, Vol: 17, ISSN: 1475-2875
BackgroundThe number of clinical cases of malaria is often recorded in resource constrained or conflict settings as a proxy for disease burden. Interpreting case count data in areas of humanitarian need is challenging due to uncertainties in population size caused by security concerns, resource constraints and population movement. Malaria prevalence in women visiting ante-natal care (ANC) clinics has the potential to be an easier and more accurate metric for malaria surveillance that is unbiased by population size if malaria testing is routinely conducted irrespective of symptoms. MethodsA suite of distributed lag non-linear models was fitted to clinical incidence time-series data in children under 5 years and ANC prevalence data from health centres run by Médecins Sans Frontières in the Democratic Republic of Congo, which implement routine intermittent screening and treatment (IST) alongside intermittent preventative treatment in pregnancy (IPTp). These statistical models enable the temporal relationship between the two metrics to be disentangled. ResultsThere was a strong relationship between the ANC prevalence and clinical incidence suggesting that both can be used to describe current malaria endemicity. There was no evidence that ANC prevalence could predict future clinical incidence, though a change in clinical incidence was shown to influence ANC prevalence up to 3 months into the future. ConclusionsThe results indicate that ANC prevalence may be a suitable metric for retrospective evaluations of the impact of malaria interventions and is a useful method for evaluating long-term malaria trends in resource constrained settings.
White MT, Walker PGT, Karl S, et al., 2018, Mathematical modelling of the impact of expanding levels of malaria control interventions on Plasmodium vivax, Nature Communications, Vol: 9, ISSN: 2041-1723
Plasmodium vivax poses unique challenges for malaria control and elimination, notably the potential for relapses to maintain transmission in the face of drug-based treatment and vector control strategies. We developed an individual-based mathematical model of P. vivax transmission calibrated to epidemiological data from Papua New Guinea (PNG). In many settings in PNG, increasing bed net coverage is predicted to reduce transmission to less than 0.1% prevalence by light microscopy, however there is substantial risk of rebounds in transmission if interventions are removed prematurely. In several high transmission settings, model simulations predict that combinations of existing interventions are not sufficient to interrupt P. vivax transmission. This analysis highlights the potential options for the future of P. vivax control: maintaining existing public health gains by keeping transmission suppressed through indefinite distribution of interventions; or continued development of strategies based on existing and new interventions to push for further reduction and towards elimination.
Routledge I, Chevez JER, Cucunubá ZM, et al., 2018, Estimating spatiotemporally varying malaria reproduction numbers in a near elimination setting, Nature Communications, Vol: 9, ISSN: 2041-1723
In 2016 the World Health Organization identified 21 countries that could eliminate malaria by 2020. Monitoring progress towards this goal requires tracking ongoing transmission. Here we develop methods that estimate individual reproduction numbers and their variation through time and space. Individual reproduction numbers, Rc, describe the state of transmission at a point in time and differ from mean reproduction numbers, which are averages of the number of people infected by a typical case. We assess elimination progress in El Salvador using data for confirmed cases of malaria from 2010 to 2016. Our results demonstrate that whilst the average number of secondary malaria cases was below one (0.61, 95% CI 0.55–0.65), individual reproduction numbers often exceeded one. We estimate a decline in Rc between 2010 and 2016. However we also show that if importation is maintained at the same rate, the country may not achieve malaria elimination by 2020.
© 2018 Wolters Kluwer Health, Inc. All rights reserved. Although the World Health Organization (WHO) has established recommendations for prevention of malaria, it remains one of the most preventable causes of adverse birth outcomes. The WHO recommends intermittent preventive treatment in pregnancy (IPTp) with for women who are HIV-negative, or co-trimoxazole prophylaxis for women who are HIV-positive. However, parasite resistance to sulfadoxine pyrimethamine in sub-Saharan Africa has led researchers to pursue other screen-and-treat approaches. This analysis reviews the effect of sulfadoxine-pyrimethamine on IPTp efficacy and summarizes trials focused on the prevention of malaria in pregnancy in areas where malaria is endemic. A total of 65 efficacy-related articles were included. Sulfadoxine-pyrimethamine as IPTp in pregnant women reduces the risk of comorbidities including anemia, antenatal and placental parasitemia, spontaneous abortions, and low birthweight. Reviews of this regimen have found it to be highly costeffective when combined with existing antenatal services. A meta-analysis conducted in Africa found that 3-course or monthly IPTp with sulfadoxine-pyrimethamine was much more effective in reducing adverse birth outcomes than the standard 2-course regimen, leading the WHO to update its guidelines in 2012. Observational studies have shown that resistance to sulfadoxine-pyrimethamine reduces the parasitological efficacy of IPTp and duration of prophylaxis. High resistance is found in regions where prevalence of parasites with quintuple Plasmodium falciparum dihydrofolate reductase (Pfdhfr) and dihydropteroate synthetase (Pfdhps) mutations is greater than 90%. Even in such locations, sulfadoxine-pyrimethamine regimens continue to have beneficial effects on low birthweight. Research into alternative IPTp therapies are ongoing, yet many proposed alternatives thus far have found that they are tolerated poorly by patients. Two trials of IPTp using dihydroart
Malaria remains one of the most preventable causes of adverse birth outcomes. Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine is used to prevent malaria, but resistance to this drug combination has decreased its efficacy and new alternatives are needed. In Africa, a meta-analysis showed three-course or monthly IPTp with sulfadoxine-pyrimethamine to be safe and more effective than the original two-course sulfadoxine-pyrimethamine strategy, prompting WHO to update its policy in 2012. Although resistance to sulfadoxine-pyrimethamine reduces the parasitological efficacy of IPTp, this drug combination remains associated with reduced incidence of low birthweight in areas where prevalence of parasites with quintuple Plasmodium falciparum dihydrofolate reductase (Pfdhfr) and dihydropteroate synthetase (Pfdhps) mutations is greater than 90%. Nevertheless, its effectiveness is compromised in women infected with sextuple mutant parasites. Six trials of IPTp showed that neither amodiaquine, mefloquine, nor chloroquine-azithromycin are suitable replacements for sulfadoxine-pyrimethamine because of poor tolerability. Furthermore, four trials showed that intermittent screening and treatment with the current generation of malaria rapid diagnostic tests was not a suitable alternative strategy to IPTp with sulfadoxine-pyrimethamine, even in areas with high prevalence of quintuple mutations. Two trials showed that IPTp with dihydroartemisinin-piperaquine was well tolerated, effective, and acceptable for IPTp, with monthly regimens being the most effective. Coverage of IPTp and insecticide-treated nets continues to lag behind targets. The key barriers to uptake are well documented, and many are open to intervention. Outside of Africa, a single trial suggests a potential role for integrated approaches that combine sulfadoxine-pyrimethamine with azithromycin for IPTp in areas of Papua New Guinea where malaria transmission is high. Modelling analysis s
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.