Publications
44 results found
Cooper LV, Erbeto TB, Danzomo AA, et al., 2024, Effectiveness of poliovirus vaccines against circulating vaccine-derived type 2 poliomyelitis in Nigeria between 2017 and 2022: a case-control study, Lancet Infectious Diseases, Vol: 24, Pages: 427-436, ISSN: 1473-3099
BackgroundBetween 2018 and 2022, Nigeria experienced continuous transmission of circulating vaccine-derived type 2 poliovirus (cVDPV2), with 526 cases of cVDPV2 poliomyelitis detected in total and approximately 180 million doses of monovalent type 2 oral poliovirus vaccine (mOPV2) and 450 million doses of novel type 2 oral poliovirus vaccine (nOPV2) delivered in outbreak response campaigns. Inactivated poliovirus vaccine (IPV) was introduced into routine immunisation in 2015, with a second dose added in 2021. We aimed to estimate the effectiveness of nOPV2 against cVDPV2 paralysis and compare nOPV2 effectiveness with that of mOPV2 and IPV.MethodsIn this retrospective case-control study, we used acute flaccid paralysis (AFP) surveillance data in Nigeria from Jan 1, 2017, to Dec 31, 2022, using age-matched, onset-matched, and location-matched cVDPV2-negative AFP cases as test-negative controls. We also did a parallel prospective study from March, 2021, using age-matched community controls from the same settlement as the cases. We included children born after May, 2016, younger than 60 months, for whom polio immunisation history (doses of OPV from campaigns and IPV) was reported. We estimated the per-dose effectiveness of nOPV2 against cVDPV2 paralysis using conditional logistic regression and compared nOPV2 effectiveness with that of mOPV2 and IPV.FindingsIn the retrospective case-control study, we identified 509 cVDPV2 poliomyelitis cases in Nigeria with case verification and paralysis onset between Jan 1, 2017, and Dec 31, 2022. Of these, 82 children were excluded for not meeting inclusion criteria, and 363 (85%) of 427 eligible cases were matched to 1303 test-negative controls. Cases reported fewer OPV and IPV doses than test-negative controls (mean number of OPV doses 5·9 [SD 4·2] in cases vs 6·7 [4·3] in controls; one or more IPV doses reported in 95 [26%] of 363 cases vs 513 [39%] of 1303 controls). We found low per-dose effect
Cooper LV, Blake IM, 2024, First Africa-based clinical trial for novel type 2 oral poliovirus vaccine., Lancet, Vol: 403, Pages: 1113-1115
Bandyopadhyay AS, Lopez Cavestany R, Blake IM, et al., 2023, Use of inactivated poliovirus vaccine for poliovirus outbreak response., Lancet Infect Dis
With continued wild poliovirus transmission in Afghanistan and Pakistan and circulating vaccine-derived poliovirus in certain countries, there exists an ongoing risk of importation of polioviruses into other countries, including those that have been polio-free for decades. Diversifying the poliovirus outbreak response toolkit is essential to account for different public health and epidemiological contexts. In this Personal View, we discuss data on intestinal and pharyngeal mucosal immunity induced by inactivated poliovirus vaccine (IPV), previous programmatic experience of poliovirus outbreak response with IPV, and outbreak response guidelines in countries that exclusively use IPV. With recent reports of poliovirus detection in polio-free countries such as the USA and the UK, it is important to assess the interplay of virus transmission dynamics, vaccine impact on preventing paralysis and virus spread, and regulatory complexities of using oral poliovirus vaccine (OPV) and IPV options for outbreak response. As the global eradication programme navigates through cessation of routine OPV use with replacement by IPV and stockpiling of novel OPVs, clarity on the impact of IPV use will be important for informed decision making by global, regional, and national policy makers.
Shaw AG, Troman C, Akello JO, et al., 2023, Defining a research agenda for environmental wastewater surveillance of pathogens, Nature Medicine, Vol: 29, Pages: 2155-2157, ISSN: 1078-8956
Wettstone EG, Islam MO, Hughlett L, et al., 2023, Interactive SARS-CoV-2 dashboard for real-time geospatial visualisation of sewage and clinical surveillance data from Dhaka, Bangladesh: a tool for public health situational awareness, BMJ Global Health, Vol: 8, Pages: 1-9, ISSN: 2059-7908
Throughout the COVID-19 pandemic, many dashboards were created to visualise clinical case incidence. Other dashboards have displayed SARS-CoV-2 sewage data, largely from countries with formal sewage networks. However, very few dashboards from low-income and lower-middle-income countries integrated both clinical and sewage data sets. We created a dashboard to track in real-time both COVID-19 clinical cases and the level of SARS-CoV-2 virus in sewage in Dhaka, Bangladesh. The development of this dashboard was a collaborative iterative process with Bangladesh public health stakeholders to include specific features to address their needs. The final dashboard product provides spatiotemporal visualisations of COVID-19 cases and SARS-CoV-2 viral load at 51 sewage collection sites in 21 wards in Dhaka since 24 March 2020. Our dashboard was updated weekly for the Bangladesh COVID-19 national task force to provide supplemental data for public health stakeholders making public policy decisions on mitigation efforts. Here, we highlight the importance of working closely with public health stakeholders to create a COVID-19 dashboard for public health impact. In the future, the dashboard can be expanded to track trends of other infectious diseases as sewage surveillance is increased for other pathogens.
Gray E, Cooper L, Bandyopadhyay A, et al., 2023, The origins and risk factors for serotype-2 vaccine-derived poliovirus (VDPV2) emergences in Africa during 2016-2019, Journal of Infectious Diseases, Vol: 228, Pages: 80-88, ISSN: 0022-1899
Serotype 2 oral poliovirus vaccine (OPV2) can revert to regain wild-type neurovirulence and spread to cause emergences of vaccine-derived poliovirus (VDPV2). After its global withdrawal from routine immunization in 2016, outbreak response use has created a cycle of VDPV2 emergences that threaten eradication. We implemented a hierarchical model based on VP1 region genetic divergence, time, and location to attribute emergences to campaigns and identify risk factors. We found that a 10 percentage point increase in population immunity in children younger than 5 years at the campaign time and location corresponds to a 18.0% decrease (95% credible interval [CrI], 6.3%–28%) in per-campaign relative risk, and that campaign size is associated with emergence risk (relative risk scaling with population size to a power of 0.80; 95% CrI, .50–1.10). Our results imply how Sabin OPV2 can be used alongside the genetically stable but supply-limited novel OPV2 (listed for emergency use in November 2020) to minimize emergence risk.
Rogawski McQuade ET, Blake I, Brennhofer SA, et al., 2023, Real-time sewage surveillance for SARS-CoV-2 in Dhaka, Bangladesh versus clinical COVID-19 surveillance: a longitudinal environmental surveillance study (Dec 2019 – Dec 2021), The Lancet Microbe, Vol: 4, Pages: e442-e451, ISSN: 2666-5247
Background: Clinical surveillance for COVID-19 has typically been challenging in low-middle income settings. From December 2019 to December 2021, we implemented environmental surveillance (ES) in a converging informal sewage network in Dhaka, Bangladesh, to investigate SARS-CoV-2 transmission across different income levels of the city compared to clinical surveillance.Methods: All sewage lines were mapped, and sites were selected with estimated catchment population of >1,000 individuals. We analysed 2,073 sewage samples, collected weekly from 37 sites and 648 days of case data from 8 wards with varying socio-economic statuses. We assessed the correlations between the viral load in sewage samples and clinical cases.Findings: SARS-CoV-2 was consistently detected across all wards (low to high income) despite large differences in reported clinical cases and periods of no cases. Most COVID-19 cases (60.3%, n=28,766/47,683) were reported from high-income areas with high levels of clinical testing (261-1603 monthly tests per 100,000 vs. 0-189 in lower-income areas), despite containing 25% (184,117/734,755) of the study population. Conversely, a similar quantity of SARS-CoV-2 was detected in sewage across different income levels (mean difference in high vs. low-income areas: 0.35 log10 viral copies + 1). The correlation between the mean sewage viral load (log10 viral copies + 1) and the log10 clinical cases increased with time (R=0.90 July 2021-December 2021 and R=0.59 July 2020-December 2020). Before major waves of infection, viral load quantity in sewage samples increased one to two weeks before the clinical cases.Interpretation: This study demonstrates the utility and importance of environmental surveillance for SARS-CoV-2 in a low-middle income country. We show ES provides an early warning of increases in transmission and shows evidence of persistent circulation in poorer areas where access to clinical testing is limited.Funding: Bill and Melinda Gates Foundation (IN
Molodecky NA, Jafari H, Safdar RM, et al., 2023, Modelling the spread of serotype-2 vaccine derived-poliovirus outbreak in Pakistan and Afghanistan to inform outbreak control strategies in the context of the COVID-19 pandemic, Vaccine, Vol: 41, Pages: A93-A104, ISSN: 0264-410X
BackgroundSince July 2019, Pakistan and Afghanistan have been facing an outbreak of serotype-2 circulating vaccine derived poliovirus (cVDPV2) in addition to continued transmission of serotype-1 wild poliovirus (WPV1) and SARS-CoV-2 in 2020. Understanding the risks of cVDPV2 transmission due to pause of global vaccination efforts and the impact of potential vaccination response strategies in the current context of COVID-19 mitigation measures is critical.MethodsWe developed a stochastic, geographically structured mathematical model of cVDPV2 transmission which captures both mucosal and humoral immunity separately and allows for reversion of serotype-2 oral polio vaccine (OPV2) virus to cVDPV2 following vaccine administration. The model includes geographic heterogeneities in vaccination coverage, population immunity and population movement. The model was fitted to historic cVDPV2 cases in Pakistan and Afghanistan between January 2010-April 2016 and July 2019-March 2020 using iterated particle filtering. The model was used to simulate spread of cVDPV2 infection from July 2019 to explore impact of various proposed vaccination responses on stopping transmission and risk of spread of reverted Sabin-2 under varying assumptions of impacts from COVID-19 lockdown measures on movement patterns as well as declines in vaccination coverage.ResultsSimulated monthly incidence of cVDPV2 from the best-fit model demonstrated general spatio-temporal alignment with observed cVDPV2 cases. The model predicted substantial spread of cVDPV2 infection, with widespread transmission through 2020 in the absence of any vaccination activities. Vaccination responses were predicted to substantially reduce transmission and case burden, with a greater impact from earlier responses and those with larger geographic scope. While the greatest risk of seeding reverted Sabin-2 was predicted in areas targeted with OPV2, subsequent spread was greatest in areas with no or delayed response. The proposed vaccin
Shaw A, Cooper L, Gumede N, et al., 2022, Time taken to detect and respond to polio outbreaks in Africa and the potential impact of direct molecular detection and nanopore sequencing, Journal of Infectious Diseases, Vol: 226, Pages: 453-462, ISSN: 0022-1899
BackgroundDetection of poliovirus outbreaks relies on a complex laboratory algorithm of cell-culture, PCR and sequencing to distinguish wild-type and vaccine-derived polioviruses (VDPV) from Sabin-like strains. We investigated the potential for direct molecular detection and nanopore sequencing (DDNS) to accelerate poliovirus detection.MethodsWe analysed laboratory data for time required to analyse and sequence serotype-2 VDPV (VDPV2) in stool collected from children with acute flaccid paralysis in Africa (May 2016-February 2020). Impact of delayed detection on VDPV2 outbreak size was assessed through negative binomial regression.ResultsVDPV2 confirmation in 525 stools required a median of 49 days from paralysis onset (10th-90th percentile: 29-74), comprising collection and transport (median: 16 days), cell-culture (7 days), intratypic differentiation RT-qPCR (3 days) and sequencing (including shipping if required) (15 days). New VDPV2 outbreaks were confirmed a median of 35 days (27-60) after paralysis onset, which we estimate could be reduced to 16 days by DDNS (9-37). Because longer delays in confirmation and response were positively associated with more cases (p<0.001), we estimate that DDNS could reduce the number of VDPV2 cases before a response by 28% (95% CrI 12-42%).ConclusionsDDNS could accelerate poliovirus outbreak response, reducing their size and the cost of eradication.
Martin J, Burns CC, Jorba J, et al., 2022, Genetic characterization of novel oral polio vaccine Type 2 viruses during initial use phase under emergency use listing-worldwide, March-October 2021, MMWR : Morbidity & Mortality Weekly Report, Vol: 71, Pages: 786-790, ISSN: 0149-2195
What is already known about this topic?Sabin oral polio vaccine virus can revert to neurovirulence in populations with low immunity. A genetically stable novel type 2 oral poliovirus vaccine (nOPV2) was authorized for outbreak response use under a World Health Organization Emergency Use Listing.What is added by this report?Global nOPV2 genomic surveillance during March–October 2021 confirmed genetic stability of the primary attenuating site.What are the implications for public health practice?nOPV2 is used to respond to poliovirus outbreaks with comparatively low risk for generating new circulating strains. Given the background immunity, population dynamics, and scale of use, the consistent pattern of genetic characteristics of nOPV2 isolates is encouraging. nOPV2 surveillance should continue for the duration of the Emergency Use Listing.
Cooper LV, Bandyopadhyay AS, Gumede N, et al., 2022, Risk factors for the spread of vaccine-derived type 2 polioviruses after global withdrawal of trivalent oral poliovirus vaccine and the effects of outbreak responses with monovalent vaccine: a retrospective analysis of surveillance data for 51 countries in Africa, Lancet Infectious Diseases, Vol: 22, Pages: 284-294, ISSN: 1473-3099
BACKGROUND: Expanding outbreaks of circulating vaccine-derived type 2 poliovirus (cVDPV2) across Africa after the global withdrawal of trivalent oral poliovirus vaccine (OPV) in 2016 are delaying global polio eradication. We aimed to assess the effect of outbreak response campaigns with monovalent type 2 OPV (mOPV2) and the addition of inactivated poliovirus vaccine (IPV) to routine immunisation. METHODS: We used vaccination history data from children under 5 years old with non-polio acute flaccid paralysis from a routine surveillance database (the Polio Information System) and setting-specific OPV immunogenicity data from the literature to estimate OPV-induced and IPV-induced population immunity against type 2 poliomyelitis between Jan 1, 2015, and June 30, 2020, for 51 countries in Africa. We investigated risk factors for reported cVDPV2 poliomyelitis including population immunity, outbreak response activities, and correlates of poliovirus transmission using logistic regression. We used the model to estimate cVDPV2 risk for each 6-month period between Jan 1, 2016, and June 30, 2020, with different numbers of mOPV2 campaigns and compared the timing and location of actual mOPV2 campaigns and the number of mOPV2 campaigns required to reduce cVDPV2 risk to low levels. FINDINGS: Type 2 OPV immunity among children under 5 years declined from a median of 87% (IQR 81-93) in January-June, 2016 to 14% (9-37) in January-June, 2020. Type 2 immunity from IPV among children under 5 years increased from 3% (<1-6%) in January-June, 2016 to 35% (24-47) in January-June, 2020. The probability of cVDPV2 poliomyelitis among children under 5 years was negatively correlated with OPV-induced and IPV-induced immunity and mOPV2 campaigns (adjusted odds ratio: OPV 0·68 [95% CrI 0·60-0·76], IPV 0·82 [0·68-0·99] per 10% absolute increase in estimated population immunity, mOPV2 0·30 [0·20-0·44] per campaign). Vaccination campaig
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.
Hamisu AW, Blake IM, Sume G, et al., 2020, Characterizing environmental surveillance sites in Nigeria and their sensitivity to detect poliovirus and other enteroviruses, The Journal of Infectious Diseases, Vol: 225, ISSN: 0022-1899
BackgroundEnvironmental surveillance (ES) for poliovirus is increasingly important for polio eradication, often detecting circulating virus before paralytic cases are reported. The sensitivity of ES depends on appropriate selection of sampling sites, which is difficult in low-income countries with informal sewage networks.MethodsWe measured ES site and sample characteristics in Nigeria during June 2018 - May 2019, including sewage physicochemical properties using a water-quality probe, flow volume, catchment population and local facilities such as hospitals, schools and transit hubs. We used mixed-effects logistic regression and machine-learning (random forests) to investigate their association with enterovirus isolation (poliovirus and non-polio enteroviruses) as an indicator of surveillance sensitivity.ResultsFour quarterly visits were made to 78 ES sites in 21 states of Nigeria, and ES site characteristic data matched to 1,345 samples with an average enterovirus prevalence among sites of 68% (range 9% to 100%). A larger estimated catchment population, high total dissolved solids and higher pH were associated with enterovirus detection. A random forests model predicted ‘good’ sites (enterovirus prevalence >70%) from measured site characteristics with out-of-sample sensitivity and specificity of 75%.ConclusionsSimple measurement of sewage properties and catchment population estimation could improve ES site selection and increase surveillance sensitivity.
Blake IM, Pons Salort M, Molodecky N, et al., 2018, Type 2 Poliovirus Detection After Global Withdrawal of Trivalent Oral Vaccine, New England Journal of Medicine, Vol: 379, Pages: 834-845, ISSN: 0028-4793
BackgroundMass campaigns with oral poliovirus vaccine (OPV) have brought the world close to the eradication of wild poliovirus. However, to complete eradication, OPV must itself be withdrawn to prevent outbreaks of vaccine-derived poliovirus (VDPV). Synchronized global withdrawal of OPV began with serotype 2 OPV (OPV2) in April 2016, which presented the first test of the feasibility of eradicating all polioviruses.MethodsWe analyzed global surveillance data on the detection of serotype 2 Sabin vaccine (Sabin-2) poliovirus and serotype 2 vaccine–derived poliovirus (VDPV2, defined as vaccine strains that are at least 0.6% divergent from Sabin-2 poliovirus in the viral protein 1 genomic region) in stool samples from 495,035 children with acute flaccid paralysis in 118 countries and in 8528 sewage samples from four countries at high risk for transmission; the samples were collected from January 1, 2013, through July 11, 2018. We used Bayesian spatiotemporal smoothing and logistic regression to identify and map risk factors for persistent detection of Sabin-2 poliovirus and VDPV2.ResultsThe prevalence of Sabin-2 poliovirus in stool samples declined from 3.9% (95% confidence interval [CI], 3.5 to 4.3) at the time of OPV2 withdrawal to 0.2% (95% CI, 0.1 to 2.7) at 2 months after withdrawal, and the detection rate in sewage samples declined from 71.0% (95% CI, 61.0 to 80.0) to 13.0% (95% CI, 8.0 to 20.0) during the same period. However, 12 months after OPV2 withdrawal, Sabin-2 poliovirus continued to be detected in stool samples (<0.1%; 95% CI, <0.1 to 0.1) and sewage samples (8.0%; 95% CI, 5.0 to 13.0) because of the use of OPV2 in response to VDPV2 outbreaks. Nine outbreaks were reported after OPV2 withdrawal and were associated with low coverage of routine immunization (odds ratio, 1.64 [95% CI, 1.14 to 2.54] per 10% absolute decrease) and low levels of population immunity (odds ratio, 2.60 [95% CI, 1.35 to 5.59] per 10% absolute decrease) within affected cou
Molodecky NAL, Blake IM, O'reilly KM, et al., 2017, Risk-factors and short-term projections for serotype-1 poliomyelitis incidence in Pakistan: a spatio-temporal analysis, Plos Medicine, Vol: 14, ISSN: 1549-1676
BackgroundPakistan currently provides a substantial challenge to global polio eradication, having contributed to 73% of reported poliomyelitis in 2015 and 54% in 2016. A better understanding of the risk factors and movement patterns that contribute to poliovirus transmission across Pakistan would support evidence-based planning for mass vaccination campaigns.Methods and findingsWe fit mixed-effects logistic regression models to routine surveillance data recording the presence of poliomyelitis associated with wild-type 1 poliovirus in districts of Pakistan over 6-month intervals between 2010 to 2016. To accurately capture the force of infection (FOI) between districts, we compared 6 models of population movement (adjacency, gravity, radiation, radiation based on population density, radiation based on travel times, and mobile-phone based). We used the best-fitting model (based on the Akaike Information Criterion [AIC]) to produce 6-month forecasts of poliomyelitis incidence. The odds of observing poliomyelitis decreased with improved routine or supplementary (campaign) immunisation coverage (multivariable odds ratio [OR] = 0.75, 95% confidence interval [CI] 0.67–0.84; and OR = 0.75, 95% CI 0.66–0.85, respectively, for each 10% increase in coverage) and increased with a higher rate of reporting non-polio acute flaccid paralysis (AFP) (OR = 1.13, 95% CI 1.02–1.26 for a 1-unit increase in non-polio AFP per 100,000 persons aged <15 years). Estimated movement of poliovirus-infected individuals was associated with the incidence of poliomyelitis, with the radiation model of movement providing the best fit to the data. Six-month forecasts of poliomyelitis incidence by district for 2013–2016 showed good predictive ability (area under the curve range: 0.76–0.98). However, although the best-fitting movement model (radiation) was a significant determinant of poliomyelitis incidence, it did not improve the predictive ability of the multivariable mo
Cori A, Donnelly CA, dorigatti, et al., 2017, Key data for outbreak evaluation: building on the Ebola experience, Philosophical Transactions of the Royal Society B: Biological Sciences, Vol: 372, ISSN: 1471-2970
Following the detection of an infectious disease outbreak, rapid epidemiological assessmentis critical to guidean effectivepublic health response. To understand the transmission dynamics and potential impact of an outbreak, several types of data are necessary. Here we build on experience gained inthe West AfricanEbolaepidemic and prior emerging infectious disease outbreaksto set out a checklist of data needed to: 1) quantify severity and transmissibility;2) characterise heterogeneities in transmission and their determinants;and 3) assess the effectiveness of different interventions.We differentiate data needs into individual-leveldata (e.g. a detailed list of reported cases), exposure data(e.g.identifying where / howcases may have been infected) and populationlevel data (e.g.size/demographicsof the population(s)affected andwhen/where interventions were implemented). A remarkable amount of individual-level and exposuredata was collected during the West African Ebola epidemic, which allowed the assessment of (1) and (2). However,gaps in population-level data (particularly around which interventions were applied whenand where)posed challenges to the assessment of (3).Herewehighlight recurrent data issues, give practical suggestions for addressingthese issues and discuss priorities for improvements in data collection in future outbreaks.
Garske T, Cori A, Ariyarajah A, et al., 2017, Heterogeneities in the case fatality ratio in the West African Ebola outbreak 2013 – 2016, Philosophical Transactions of the Royal Society B: Biological Sciences, Vol: 372, ISSN: 1471-2970
The 2013–2016 Ebola outbreak in West Africa is the largest on record with 28 616 confirmed, probable and suspected cases and 11 310 deaths officially recorded by 10 June 2016, the true burden probably considerably higher. The case fatality ratio (CFR: proportion of cases that are fatal) is a key indicator of disease severity useful for gauging the appropriate public health response and for evaluating treatment benefits, if estimated accurately. We analysed individual-level clinical outcome data from Guinea, Liberia and Sierra Leone officially reported to the World Health Organization. The overall mean CFR was 62.9% (95% CI: 61.9% to 64.0%) among confirmed cases with recorded clinical outcomes. Age was the most important modifier of survival probabilities, but country, stage of the epidemic and whether patients were hospitalized also played roles. We developed a statistical analysis to detect outliers in CFR between districts of residence and treatment centres (TCs), adjusting for known factors influencing survival and identified eight districts and three TCs with a CFR significantly different from the average. From the current dataset, we cannot determine whether the observed variation in CFR seen by district or treatment centre reflects real differences in survival, related to the quality of care or other factors or was caused by differences in reporting practices or case ascertainment.
Nouvellet P, Cori A, Garske T, et al., 2017, A simple approach to measure transmissibility and forecast incidence, Epidemics, Vol: 22, Pages: 29-35, ISSN: 1755-4365
Outbreaks of novel pathogens such as SARS, pandemic influenza and Ebola require substantial investments in reactive interventions, with consequent implementation plans sometimes revised on a weekly basis. Therefore, short-term forecasts of incidence are often of high priority. In light of the recent Ebola epidemic in West Africa, a forecasting exercise was convened by a network of infectious disease modellers. The challenge was to forecast unseen “future” simulated data for four different scenarios at five different time points. In a similar method to that used during the recent Ebola epidemic, we estimated current levels of transmissibility, over variable time-windows chosen in an ad hoc way. Current estimated transmissibility was then used to forecast near-future incidence. We performed well within the challenge and often produced accurate forecasts. A retrospective analysis showed that our subjective method for deciding on the window of time with which to estimate transmissibility often resulted in the optimal choice. However, when near-future trends deviated substantially from exponential patterns, the accuracy of our forecasts was reduced. This exercise highlights the urgent need for infectious disease modellers to develop more robust descriptions of processes – other than the widespread depletion of susceptible individuals – that produce non-exponential patterns of incidence.
International Ebola Response Team, Agua-Agum J, Ariyarajah A, et al., 2016, Exposure patterns driving Ebola transmissions in West Africa: a retrospective observational study, PLOS Medicine, Vol: 13, ISSN: 1549-1277
BACKGROUND: The ongoing West African Ebola epidemic began in December 2013 in Guinea, probably from a single zoonotic introduction. As a result of ineffective initial control efforts, an Ebola outbreak of unprecedented scale emerged. As of 4 May 2015, it had resulted in more than 19,000 probable and confirmed Ebola cases, mainly in Guinea (3,529), Liberia (5,343), and Sierra Leone (10,746). Here, we present analyses of data collected during the outbreak identifying drivers of transmission and highlighting areas where control could be improved.METHODS AND FINDINGS: Over 19,000 confirmed and probable Ebola cases were reported in West Africa by 4 May 2015. Individuals with confirmed or probable Ebola ("cases") were asked if they had exposure to other potential Ebola cases ("potential source contacts") in a funeral or non-funeral context prior to becoming ill. We performed retrospective analyses of a case line-list, collated from national databases of case investigation forms that have been reported to WHO. These analyses were initially performed to assist WHO's response during the epidemic, and have been updated for publication. We analysed data from 3,529 cases in Guinea, 5,343 in Liberia, and 10,746 in Sierra Leone; exposures were reported by 33% of cases. The proportion of cases reporting a funeral exposure decreased over time. We found a positive correlation (r = 0.35, p < 0.001) between this proportion in a given district for a given month and the within-district transmission intensity, quantified by the estimated reproduction number (R). We also found a negative correlation (r = -0.37, p < 0.001) between R and the district proportion of hospitalised cases admitted within ≤4 days of symptom onset. These two proportions were not correlated, suggesting that reduced funeral attendance and faster hospitalisation independently influenced local transmission intensity. We were able to identify 14% of potential source contacts as cases in the
Pons-Salort M, Molodecky NA, O'Reilly KM, et al., 2016, Population immunity against serotype-2 poliomyelitis Leading up to the global withdrawal of the oral poliovirus vaccine: spatio-temporal modelling of surveillance data, Plos Medicine, Vol: 13, ISSN: 1549-1676
BackgroundGlobal withdrawal of serotype-2 oral poliovirus vaccine (OPV2) took place in April 2016. This marked a milestone in global polio eradication and was a public health intervention of unprecedented scale, affecting 155 countries. Achieving high levels of serotype-2 population immunity before OPV2 withdrawal was critical to avoid subsequent outbreaks of serotype-2 vaccine-derived polioviruses (VDPV2s).Methods and FindingsIn August 2015, we estimated vaccine-induced population immunity against serotype-2 poliomyelitis for 1 January 2004–30 June 2015 and produced forecasts for April 2016 by district in Nigeria and Pakistan. Population immunity was estimated from the vaccination histories of children <36 mo old identified with non-polio acute flaccid paralysis (AFP) reported through polio surveillance, information on immunisation activities with different oral poliovirus vaccine (OPV) formulations, and serotype-specific estimates of the efficacy of these OPVs against poliomyelitis. District immunity estimates were spatio-temporally smoothed using a Bayesian hierarchical framework. Coverage estimates for immunisation activities were also obtained, allowing for heterogeneity within and among districts. Forward projections of immunity, based on these estimates and planned immunisation activities, were produced through to April 2016 using a cohort model.Estimated population immunity was negatively correlated with the probability of VDPV2 poliomyelitis being reported in a district. In Nigeria and Pakistan, declines in immunity during 2008–2009 and 2012–2013, respectively, were associated with outbreaks of VDPV2. Immunity has since improved in both countries as a result of increased use of trivalent OPV, and projections generally indicated sustained or improved immunity in April 2016, such that the majority of districts (99% [95% uncertainty interval 97%–100%] in Nigeria and 84% [95% uncertainty interval 77%–91%] in Pakistan) had >70
Pinsent A, Blake IM, Basáñez MG, et al., 2016, Mathematical Modelling of Trachoma Transmission, Control and Elimination., Publisher: Elsevier, Pages: 1-48
The World Health Organization has targeted the elimination of blinding trachoma by the year 2020. To this end, the Global Elimination of Blinding Trachoma (GET, 2020) alliance relies on a four-pronged approach, known as the SAFE strategy (S for trichiasis surgery; A for antibiotic treatment; F for facial cleanliness and E for environmental improvement). Well-constructed and parameterized mathematical models provide useful tools that can be used in policy making and forecasting in order to help to control trachoma and understand the feasibility of this large-scale elimination effort. As we approach this goal, the need to understand the transmission dynamics of infection within areas of different endemicities, to optimize available resources and to identify which strategies are the most cost-effective becomes more pressing. In this study, we conducted a review of the modelling literature for trachoma and identified 23 articles that included a mechanistic or statistical model of the transmission, dynamics and/or control of (ocular) Chlamydia trachomatis. Insights into the dynamics of trachoma transmission have been generated through both deterministic and stochastic models. A large body of the modelling work conducted to date has shown that, to varying degrees of effectiveness, antibiotic administration can reduce or interrupt trachoma transmission. However, very little analysis has been conducted to consider the effect of nonpharmaceutical interventions (and particularly the F and E components of the SAFE strategy) in helping to reduce transmission. Furthermore, very few of the models identified in the literature review included a structure that permitted tracking of the prevalence of active disease (in the absence of active infection) and the subsequent progression to disease sequelae (the morbidity associated with trachoma and ultimately the target of GET 2020 goals). This represents a critical gap in the current trachoma modelling literature, which m
Agua-Agum J, Allegranzi B, Ariyarajah A, et al., 2016, After Ebola in West Africa - Unpredictable Risks, Preventable Epidemics, New England Journal of Medicine, Vol: 375, Pages: 587-596, ISSN: 1533-4406
Between December 2013 and April 2016, the largest epidemic of Ebola virus disease (EVD) to date generated more than 28,000 cases and more than 11,000 deaths in the large, mobile populations of Guinea, Liberia, and Sierra Leone. Tracking the rapid rise and slower decline of the West African epidemic has reinforced some common understandings about the epidemiology and control of EVD but has also generated new insights. Despite having more information about the geographic distribution of the disease, the risk of human infection from animals and from survivors of EVD remains unpredictable over a wide area of equatorial Africa. Until human exposure to infection can be anticipated or avoided, future outbreaks will have to be managed with the classic approach to EVD control — extensive surveillance, rapid detection and diagnosis, comprehensive tracing of contacts, prompt patient isolation, supportive clinical care, rigorous efforts to prevent and control infection, safe and dignified burial, and engagement of the community. Empirical and modeling studies conducted during the West African epidemic have shown that large epidemics of EVD are preventable — a rapid response can interrupt transmission and restrict the size of outbreaks, even in densely populated cities. The critical question now is how to ensure that populations and their health services are ready for the next outbreak, wherever it may occur. Health security across Africa and beyond depends on committing resources to both strengthen national health systems and sustain investment in the next generation of vaccines, drugs, and diagnostics.
Pons-Salort M, Burns CC, Lyons H, et al., 2016, Preventing Vaccine-Derived Poliovirus Emergence during the Polio Endgame, PLOS Pathogens, Vol: 12, ISSN: 1553-7366
Reversion and spread of vaccine-derived poliovirus (VDPV) to cause outbreaks of poliomyelitis is a rare outcome resulting from immunisation with the live-attenuated oral poliovirus vaccines (OPVs). Global withdrawal of all three OPV serotypes is therefore a key objective of the polio endgame strategic plan, starting with serotype 2 (OPV2) in April 2016. Supplementary immunisation activities (SIAs) with trivalent OPV (tOPV) in advance of this date could mitigate the risks of OPV2 withdrawal by increasing serotype-2 immunity, but may also create new serotype-2 VDPV (VDPV2). Here, we examine the risk factors for VDPV2 emergence and implications for the strategy of tOPV SIAs prior to OPV2 withdrawal. We first developed mathematical models of VDPV2 emergence and spread. We found that in settings with low routine immunisation coverage, the implementation of a single SIA increases the risk of VDPV2 emergence. If routine coverage is 20%, at least 3 SIAs are needed to bring that risk close to zero, and if SIA coverage is low or there are persistently "missed" groups, the risk remains high despite the implementation of multiple SIAs. We then analysed data from Nigeria on the 29 VDPV2 emergences that occurred during 2004-2014. Districts reporting the first case of poliomyelitis associated with a VDPV2 emergence were compared to districts with no VDPV2 emergence in the same 6-month period using conditional logistic regression. In agreement with the model results, the odds of VDPV2 emergence decreased with higher routine immunisation coverage (odds ratio 0.67 for a 10% absolute increase in coverage [95% confidence interval 0.55-0.82]). We also found that the probability of a VDPV2 emergence resulting in poliomyelitis in >1 child was significantly higher in districts with low serotype-2 population immunity. Our results support a strategy of focused tOPV SIAs before OPV2 withdrawal in areas at risk of VDPV2 emergence and in sufficient number to raise population immuni
Blake IM, Chenoweth P, Okayasu H, et al., 2016, Faster Detection of Poliomyelitis Outbreaks to Support Polio Eradication, Emerging Infectious Diseases, Vol: 22, Pages: 449-456, ISSN: 1080-6040
As the global eradication of poliomyelitis approaches the final stages, prompt detection of new outbreaks is critical to enable a fast and effective outbreak response. Surveillance relies on reporting of acute flaccid paralysis (AFP) cases and laboratory confirmation through isolation of poliovirus from stool. However, delayed sample collection and testing can delay outbreak detection. We investigated whether weekly testing for clusters of AFP by location and time, using the Kulldorff scan statistic, could provide an early warning for outbreaks in 20 countries. A mixed-effects regression model was used to predict background rates of nonpolio AFP at the district level. In Tajikistan and Congo, testing for AFP clusters would have resulted in an outbreak warning 39 and 11 days, respectively, before official confirmation of large outbreaks. This method has relatively high specificity and could be integrated into the current polio information system to support rapid outbreak response activities.
Agua-Agum J, Ariyarajah A, Blake IM, et al., 2016, Ebola virus disease among male and female persons in West Africa, New England Journal of Medicine, Vol: 374, Pages: 96-98, ISSN: 1533-4406
Gambhir M, Grassly NC, Burton MJ, et al., 2015, Estimating the Future Impact of a Multi-Pronged Intervention Strategy on Ocular Disease Sequelae Caused by Trachoma: A Modeling Study, Ophthalmic Epidemiology, Vol: 22, Pages: 394-402, ISSN: 1744-5086
Purpose: Trachoma control programs are underway in endemic regions worldwide. They are based on the SAFE strategy (Surgery for trichiasis, Antibiotic distribution, Facial cleanliness, and Environmental improvement). Although much is known about the effect of community-wide treatment with antibiotics on the prevalence of Chlamydia trachomatis, the impact of the SAFE strategy on severe ocular disease sequelae (the main focus of the Global Elimination of blinding Trachoma by 2020 program) remains largely unknown.Methods: We use a mathematical model to explore the impact of each of the components of the SAFE strategy, individually and together, on disease sequelae, arising from repeat infection and subsequent conjunctival scarring. We ask whether two elimination goals, to reduce the prevalence of trachomatous trichiasis to 1 per 1000 persons, and the incidence of corneal opacity to 1 per 10,000 persons per annum, are achievable, and which combinations of interventions have the greatest impact on these indicators.Results: In high prevalence communities (here, >20% infection of children aged 1–9 years), a combination of efforts is needed to bring down sustainably the prevalence and incidence of ocular disease sequelae.Conclusion: The mass delivery of antibiotics is highly beneficial for the clearance of infection, inflammation and prevention of subsequent scarring, but needs to be supplemented with sustained reductions in transmission and surgery to consider realistically the elimination of blindness by the year 2020.
Nouvellet P, Garske T, Mills HL, et al., 2015, The role of rapid diagnostics in managing Ebola epidemics, Nature, Vol: 528, Pages: S109-S116, ISSN: 0028-0836
Ebola emerged in West Africa around December 2013 and swept through Guinea, Sierra Leone and Liberia, giving rise to 27,748 confirmed, probable and suspected cases reported by 29 July 2015. Case diagnoses during the epidemic have relied on polymerase chain reaction-based tests. Owing to limited laboratory capacity and local transport infrastructure, the delays from sample collection to test results being available have often been 2 days or more. Point-of-care rapid diagnostic tests offer the potential to substantially reduce these delays. We review Ebola rapid diagnostic tests approved by the World Health Organization and those currently in development. Such rapid diagnostic tests could allow early triaging of patients, thereby reducing the potential for nosocomial transmission. In addition, despite the lower test accuracy, rapid diagnostic test-based diagnosis may be beneficial in some contexts because of the reduced time spent by uninfected individuals in health-care settings where they may be at increased risk of infection; this also frees up hospital beds. We use mathematical modelling to explore the potential benefits of diagnostic testing strategies involving rapid diagnostic tests alone and in combination with polymerase chain reaction testing. Our analysis indicates that the use of rapid diagnostic tests with sensitivity and specificity comparable with those currently under development always enhances control, whether evaluated at a health-care-unit or population level. If such tests had been available throughout the recent epidemic, we estimate, for Sierra Leone, that their use in combination with confirmatory polymerase chain-reaction testing might have reduced the scale of the epidemic by over a third.
Lipsitch M, Donnelly CA, Fraser C, et al., 2015, Potential biases in estimating absolute and relative case-fatality risks during outbreaks, PLOS Neglected Tropical Diseases, Vol: 9, ISSN: 1935-2735
Agua-Agum J, Ariyarajah A, Blake IM, et al., 2015, Ebola virus disease among children in West Africa, New England Journal of Medicine, Vol: 372, Pages: 1274-1277, ISSN: 1533-4406
Agua-Agum J, Ariyarajah A, Aylward B, et al., 2015, West African Ebola epidemic after one year - slowing but not yet under control, New England Journal of Medicine, Vol: 372, Pages: 584-587, ISSN: 1533-4406
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