Publications
73 results found
Subissi L, von Gottberg A, Thukral L, et al., 2022, An early warning system for emerging SARS-CoV-2 variants, NATURE MEDICINE, Vol: 28, Pages: 1110-1115, ISSN: 1078-8956
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- Citations: 22
Dighe A, Jombart T, Van Kerkhove MD, et al., 2019, A systematic review of MERS-CoV seroprevalence and RNA prevalence in dromedary camels: implications for animal vaccination, Epidemics, Vol: 29, ISSN: 1755-4365
Human infection with Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is driven by recurring dromedary-to-human spill-over events, leading decision-makers to consider dromedary vaccination. Dromedary vaccine candidates in the development pipeline are showing hopeful results, but gaps in our understanding of the epidemiology of MERS-CoV in dromedaries must be addressed to design and evaluate potential vaccination strategies. We aim to bring together existing measures of MERS-CoV infection in dromedary camels to assess the distribution of infection, highlighting knowledge gaps and implications for animal vaccination. We systematically reviewed the published literature on MEDLINE, EMBASE and Web of Science that reported seroprevalence and/or prevalence of active MERS-CoV infection in dromedary camels from both cross-sectional and longitudinal studies. 60 studies met our eligibility criteria. Qualitative syntheses determined that MERS-CoV seroprevalence increased with age up to 80–100% in adult dromedaries supporting geographically widespread endemicity of MERS-CoV in dromedaries in both the Arabian Peninsula and countries exporting dromedaries from Africa. The high prevalence of active infection measured in juveniles and at sites where dromedary populations mix should guide further investigation – particularly of dromedary movement – and inform vaccination strategy design and evaluation through mathematical modelling.
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.
Arabi YM, Balkhy HH, Hayden FG, et al., 2017, Middle East Respiratory Syndrome, NEW ENGLAND JOURNAL OF MEDICINE, Vol: 376, Pages: 584-594, ISSN: 0028-4793
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- Citations: 285
Horby PW, Laurie KL, Cowling BJ, et al., 2017, CONSISE statement on the reporting of Seroepidemiologic Studies for influenza (ROSES-I statement): an extension of the STROBE statement, INFLUENZA AND OTHER RESPIRATORY VIRUSES, Vol: 11, Pages: 2-14, ISSN: 1750-2640
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- Citations: 24
Van Kerkhove MD, Reveiz L, Souza JP, et al., 2016, Harmonisation of Zika virus research protocols to address key public health concerns, LANCET GLOBAL HEALTH, Vol: 4, Pages: E911-E912, ISSN: 2214-109X
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- Citations: 13
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
Ly S, Vong S, Cavailler P, et al., 2016, Environmental contamination and risk factors for transmission of highly pathogenic avian influenza A(H5N1) to humans, Cambodia, 2006-2010, BMC INFECTIOUS DISEASES, Vol: 16, ISSN: 1471-2334
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- Citations: 12
Van Kerkhove MD, Peiris MJS, Malik MR, et al., 2016, Interpreting Results From Environmental Contamination Studies of Middle East Respiratory Syndrome Coronavirus, CLINICAL INFECTIOUS DISEASES, Vol: 63, Pages: 1142-1142, ISSN: 1058-4838
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- Citations: 5
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.
Cauchemez S, Nouvellet P, Cori A, et al., 2016, Unraveling the drivers of MERS-CoV transmission., Proceedings of the National Academy of Sciences of the United States of America, Vol: 113, Pages: 9081-9086, ISSN: 1091-6490
With more than 1,700 laboratory-confirmed infections, Middle East respiratory syndrome coronavirus (MERS-CoV) remains a significant threat for public health. However, the lack of detailed data on modes of transmission from the animal reservoir and between humans means that the drivers of MERS-CoV epidemics remain poorly characterized. Here, we develop a statistical framework to provide a comprehensive analysis of the transmission patterns underlying the 681 MERS-CoV cases detected in the Kingdom of Saudi Arabia (KSA) between January 2013 and July 2014. We assess how infections from the animal reservoir, the different levels of mixing, and heterogeneities in transmission have contributed to the buildup of MERS-CoV epidemics in KSA. We estimate that 12% [95% credible interval (CI): 9%, 15%] of cases were infected from the reservoir, the rest via human-to-human transmission in clusters (60%; CI: 57%, 63%), within (23%; CI: 20%, 27%), or between (5%; CI: 2%, 8%) regions. The reproduction number at the start of a cluster was 0.45 (CI: 0.33, 0.58) on average, but with large SD (0.53; CI: 0.35, 0.78). It was >1 in 12% (CI: 6%, 18%) of clusters but fell by approximately one-half (47% CI: 34%, 63%) its original value after 10 cases on average. The ongoing exposure of humans to MERS-CoV from the reservoir is of major concern, given the continued risk of substantial outbreaks in health care systems. The approach we present allows the study of infectious disease transmission when data linking cases to each other remain limited and uncertain.
Modjarrad K, Moorthy VS, Ben Embarek P, et al., 2016, A roadmap for MERS-CoV research and product development: report from a World Health Organization consultation, NATURE MEDICINE, Vol: 22, Pages: 701-705, ISSN: 1078-8956
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- Citations: 46
Cauchemez S, Besnard M, Bompard P, et al., 2016, Association between Zika virus and microcephaly in French Polynesia, 2013-15: a retrospective study, LANCET, Vol: 387, Pages: 2125-2132, ISSN: 0140-6736
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- Citations: 610
Arabi YM, Balkhy HH, Hayden FG, et al., 2016, The search for therapeutic options for Middle East Respiratory Syndrome (MERS), JOURNAL OF INFECTION AND PUBLIC HEALTH, Vol: 9, Pages: 213-215, ISSN: 1876-0341
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- Citations: 2
Lessler J, Salje H, van Kerkhove M, et al., 2016, Estimating the Severity and Subclinical Burden of Middle East Respiratory Syndrome Coronavirus Infection in the Kingdom of Saudi Arabia, American Journal of Epidemiology, Vol: 183, Pages: 657-663, ISSN: 1476-6256
Not all persons infected with Middle East respiratory syndrome coronavirus (MERS-CoV) develop severe symptoms, which likely leads to an underestimation of the number of people infected and an overestimation of the severity. To estimate the number of MERS-CoV infections that have occurred in the Kingdom of Saudi Arabia, we applied a statistical model to a line list describing 721 MERS-CoV infections detected between June 7, 2012, and July 25, 2014. We estimated that 1,528 (95% confidence interval (CI): 1,327, 1,883) MERS-CoV infections occurred in this interval, which is 2.1 (95% CI: 1.8, 2.6) times the number reported. The probability of developing symptoms ranged from 11% (95% CI: 4, 25) in persons under 10 years of age to 88% (95% CI: 72, 97) in those 70 years of age or older. An estimated 22% (95% CI: 18, 25) of those infected with MERS-CoV died. MERS-CoV is deadly, but this work shows that its clinical severity differs markedly between groups and that many cases likely go undiagnosed.
Arabi YM, Fowler R, Bright RA, et al., 2016, Knowledge gaps in therapeutic and non-therapeutic research on the Middle East respiratory syndrome, LANCET RESPIRATORY MEDICINE, Vol: 4, Pages: 93-94, ISSN: 2213-2600
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- Citations: 3
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
Van Kerkhove MD, Cooper MJ, Cost AA, et al., 2015, Risk factors for severe outcomes among members of the United States military hospitalized with pneumonia and influenza, 2000-2012, VACCINE, Vol: 33, Pages: 6970-6976, ISSN: 0264-410X
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- Citations: 14
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
Laurie KL, Engelhardt OG, Wood J, et al., 2015, International Laboratory Comparison of Influenza Microneutralization Assays for A(H1N1) pdm09, A(H3N2), and A(H5N1) Influenza Viruses by CONSISE, Clinical and Vaccine Immunology, Vol: 22, Pages: 957-964, ISSN: 1556-6811
The microneutralization assay is commonly used to detect antibodies to influenza virus, and multiple protocols are used worldwide. These protocols differ in the incubation time of the assay as well as in the order of specific steps, and even within protocols there are often further adjustments in individual laboratories. The impact these protocol variations have on influenza serology data is unclear. Thus, a laboratory comparison of the 2-day enzyme-linked immunosorbent assay (ELISA) and 3-day hemagglutination (HA) microneutralization (MN) protocols, using A(H1N1)pdm09, A(H3N2), and A(H5N1) viruses, was performed by the CONSISE Laboratory Working Group. Individual laboratories performed both assay protocols, on multiple occasions, using different serum panels. Thirteen laboratories from around the world participated. Within each laboratory, serum sample titers for the different assay protocols were compared between assays to determine the sensitivity of each assay and were compared between replicates to assess the reproducibility of each protocol for each laboratory. There was good correlation of the results obtained using the two assay protocols in most laboratories, indicating that these assays may be interchangeable for detecting antibodies to the influenza A viruses included in this study. Importantly, participating laboratories have aligned their methodologies to the CONSISE consensus 2-day ELISA and 3-day HA MN assay protocols to enable better correlation of these assays in the future.
Van Kerkhove MD, Bento AI, Mills HL, et al., 2015, A review of epidemiological parameters from Ebola outbreaks to inform early public health decision-making., Scientific Data, Vol: 2, Pages: 150019-150019, ISSN: 2052-4463
The unprecedented scale of the Ebola outbreak in West Africa has, as of 29 April 2015, resulted in more than 10,884 deaths among 26,277 cases. Prior to the ongoing outbreak, Ebola virus disease (EVD) caused relatively small outbreaks (maximum outbreak size 425 in Gulu, Uganda) in isolated populations in central Africa. Here, we have compiled a comprehensive database of estimates of epidemiological parameters based on data from past outbreaks, including the incubation period distribution, case fatality rate, basic reproduction number (R 0 ), effective reproduction number (R t ) and delay distributions. We have compared these to parameter estimates from the ongoing outbreak in West Africa. The ongoing outbreak, because of its size, provides a unique opportunity to better understand transmission patterns of EVD. We have not performed a meta-analysis of the data, but rather summarize the estimates by virus from comprehensive investigations of EVD and Marburg outbreaks over the past 40 years. These estimates can be used to parameterize transmission models to improve understanding of initial spread of EVD outbreaks and to inform surveillance and control guidelines.
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
Lessler J, Rodriguez-Barraquer I, Cummings T, et al., 2014, Estimating potential incidence of MERS-CoV associated with Hajj pilgrims to Saudi Arabia, 2014, PLoS Currents, Vol: Edition 1, ISSN: 2157-3999
Between March and June 2014 the Kingdom of Saudi Arabia (KSA) had a large outbreak of MERS-CoV, renewing fears of a major outbreak during the Hajj this October. Using KSA Ministry of Health data, the MERS-CoV Scenario and Modeling Working Group forecast incidence under three scenarios. In the expected incidence scenario, we estimate 6.2 (95% Prediction Interval [PI]: 1–17) pilgrims will develop MERS-CoV symptoms during the Hajj, and 4.0 (95% PI: 0–12) foreign pilgrims will be infected but return home before developing symptoms. In the most pessimistic scenario, 47.6 (95% PI: 32–66) cases will develop symptoms during the Hajj, and 29.0 (95% PI: 17–43) will be infected but return home asymptomatic. Large numbers of MERS-CoV cases are unlikely to occur during the 2014 Hajj even under pessimistic assumptions, but careful monitoring is still needed to detect possible mass infection events and minimize introductions into other countries.
WHO Ebola Response Team, 2014, Ebola virus disease in West Africa — The first 9 months of the epidemic and forward projections, New England Journal of Medicine, Vol: 371, Pages: 1481-1495, ISSN: 0028-4793
BACKGROUNDOn March 23, 2014, the World Health Organization (WHO) was notified of an outbreak of Ebola virus disease (EVD) in Guinea. On August 8, the WHO declared the epidemic to be a “public health emergency of international concern.”METHODSBy September 14, 2014, a total of 4507 probable and confirmed cases, including 2296 deaths from EVD (Zaire species) had been reported from five countries in West Africa — Guinea, Liberia, Nigeria, Senegal, and Sierra Leone. We analyzed a detailed subset of data on 3343 confirmed and 667 probable Ebola cases collected in Guinea, Liberia, Nigeria, and Sierra Leone as of September 14.RESULTSThe majority of patients are 15 to 44 years of age (49.9% male), and we estimate that the case fatality rate is 70.8% (95% confidence interval [CI], 69 to 73) among persons with known clinical outcome of infection. The course of infection, including signs and symptoms, incubation period (11.4 days), and serial interval (15.3 days), is similar to that reported in previous outbreaks of EVD. On the basis of the initial periods of exponential growth, the estimated basic reproduction numbers (R0) are 1.71 (95% CI, 1.44 to 2.01) for Guinea, 1.83 (95% CI, 1.72 to 1.94) for Liberia, and 2.02 (95% CI, 1.79 to 2.26) for Sierra Leone. The estimated current reproduction numbers (R) are 1.81 (95% CI, 1.60 to 2.03) for Guinea, 1.51 (95% CI, 1.41 to 1.60) for Liberia, and 1.38 (95% CI, 1.27 to 1.51) for Sierra Leone; the corresponding doubling times are 15.7 days (95% CI, 12.9 to 20.3) for Guinea, 23.6 days (95% CI, 20.2 to 28.2) for Liberia, and 30.2 days (95% CI, 23.6 to 42.3) for Sierra Leone. Assuming no change in the control measures for this epidemic, by November 2, 2014, the cumulative reported numbers of confirmed and probable cases are predicted to be 5740 in Guinea, 9890 in Liberia, and 5000 in Sierra Leone, exceeding 20,000 in total.CONCLUSIONSThese data indicate that without drastic improvements in control measures, the numbers of
Garske T, Van Kerkhove MD, Yactayo S, et al., 2014, Yellow Fever in Africa: Estimating the Burden of Disease and Impact of Mass Vaccination from Outbreak and Serological Data, PLoS Medicine, Vol: 11, ISSN: 1548-7091
BackgroundYellow fever is a vector-borne disease affecting humans and non-human primates in tropical areas of Africa and South America. While eradication is not feasible due to the wildlife reservoir, large scale vaccination activities in Africa during the 1940s to 1960s reduced yellow fever incidence for several decades. However, after a period of low vaccination coverage, yellow fever has resurged in the continent. Since 2006 there has been substantial funding for large preventive mass vaccination campaigns in the most affected countries in Africa to curb the rising burden of disease and control future outbreaks. Contemporary estimates of the yellow fever disease burden are lacking, and the present study aimed to update the previous estimates on the basis of more recent yellow fever occurrence data and improved estimation methods.Methods and FindingsGeneralised linear regression models were fitted to a dataset of the locations of yellow fever outbreaks within the last 25 years to estimate the probability of outbreak reports across the endemic zone. Environmental variables and indicators for the surveillance quality in the affected countries were used as covariates. By comparing probabilities of outbreak reports estimated in the regression with the force of infection estimated for a limited set of locations for which serological surveys were available, the detection probability per case and the force of infection were estimated across the endemic zone.The yellow fever burden in Africa was estimated for the year 2013 as 130,000 (95% CI 51,000–380,000) cases with fever and jaundice or haemorrhage including 78,000 (95% CI 19,000–180,000) deaths, taking into account the current level of vaccination coverage. The impact of the recent mass vaccination campaigns was assessed by evaluating the difference between the estimates obtained for the current vaccination coverage and for a hypothetical scenario excluding these vaccination campaigns. Vaccination campaign
Cauchemez S, Van Kerkhove MD, Archer BN, et al., 2014, School closures during the 2009 influenza pandemic: national and local experiences, BMC INFECTIOUS DISEASES, Vol: 14
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Kucharski A, Mills H, Pinsent A, et al., 2014, Distinguishing Between Reservoir Exposure and Human-to-Human Transmission for Emerging Pathogens Using Case Onset Data., PLoS Curr, Vol: 6
Pathogens such as MERS-CoV, influenza A/H5N1 and influenza A/H7N9 are currently generating sporadic clusters of spillover human cases from animal reservoirs. The lack of a clear human epidemic suggests that the basic reproductive number R0 is below or very close to one for all three infections. However, robust cluster-based estimates for low R0 values are still desirable so as to help prioritise scarce resources between different emerging infections and to detect significant changes between clusters and over time. We developed an inferential transmission model capable of distinguishing the signal of human-to-human transmission from the background noise of direct spillover transmission (e.g. from markets or farms). By simulation, we showed that our approach could obtain unbiased estimates of R0, even when the temporal trend in spillover exposure was not fully known, so long as the serial interval of the infection and the timing of a sudden drop in spillover exposure were known (e.g. day of market closure). Applying our method to data from the three largest outbreaks of influenza A/H7N9 outbreak in China in 2013, we found evidence that human-to-human transmission accounted for 13% (95% credible interval 1%-32%) of cases overall. We estimated R0 for the three clusters to be: 0.19 in Shanghai (0.01-0.49), 0.29 in Jiangsu (0.03-0.73); and 0.03 in Zhejiang (0.00-0.22). If a reliable temporal trend for the spillover hazard could be estimated, for example by implementing widespread routine sampling in sentinel markets, it should be possible to estimate sub-critical values of R0 even more accurately. Should a similar strain emerge with R0>1, these methods could give a real-time indication that sustained transmission is occurring with well-characterised uncertainty.
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