Correspondence Paul K Drain [email protected] Medical Practice Evaluation Center, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA 1 2 3 4 5 Westcott L. CDC Director draws parallels between Ebola outbreak and HIV/AIDS epidemic. Newsweek (USA), Oct 9, 2014. http://www.newsweek.com/cdc-directordraws-parallels-between-ebola-outbreak-andhivaids-epidemic-276466 (accessed Nov 14, 2014). Drain PK, Hyle EP, Noubary F, et al. Diagnostic point-of-care tests in resource-limited settings. Lancet Infect Dis 2014; 14: 239–49. Vogel G. Testing new Ebola tests. Science 2014; 345: 1549. WHO. UNAIDS report shows that 19 million of the 35 million people living with HIV today do not know that they have the virus (press release). Geneva: World Health Organization. July 16, 2014. http://www.unaids.org/en/ resources/presscentre/ pressreleaseandstatementarchive/2014/ july/20140716prgapreport/ (accessed Nov 14, 2014). WHO Ebola Response Team. Ebola virus disease in West Africa—the ﬁrst 9 months of the epidemic and forward projections. N Engl J Med 2014; 371: 1481–95. Ebola: between mathematics and reality Ebola needs to be contained. Despite this basic epidemiological truth, we have diﬃculty understanding the intelligence, money, and institutional eﬀorts dedicated to this disease. In their Article on the control of Ebola virus transmission, Joseph Lewnard and colleagues1 conclude that 4800 additional beds could save many lives in Montserrado, Liberia. They estimated that expanding treatment centres on Oct 15 could have prevented 137 432 cases by Dec 15. By contrast, they predicted 170 996 cases over the same period if treatment was not expanded. During that time (106 days), therefore, their projections argue that an additional 4800 beds would have treated 33 564 patients. In fact, this was a ten times overprojection. www.thelancet.com/infection Vol 15 February 2015 In our resource-depleted hospital, we treat up to 95 000 inpatients per year2 with 1300 beds; equivalent to 27 500 patients per 106 days. This care includes some quite complex treatments such as ventilation, dialysis, paediatric surgery, neurosurgery, and chemotherapy. 40% of our patients are HIV positive and need complicated schemes to deal with tuberculosis, cryptococcosis, and Kaposi´s sarcoma. Many of these patients stay in hospital longer than do Ebola patients. We cannot see why we would need 369% of our present number of beds to treat almost the same number of patients for a disease that is relatively easy to treat (even when the protective gear can be unpleasant to wear). Working daily with existing pandemic conditions such as malaria, sepsis, and road traﬃc accidents— which have killed more patients in the past 2 weeks than Ebola, severe acute respiratory syndrome, Middle East respiratory syndrome, bird ﬂu, and swine ﬂu combined in human history— we ﬁnd it diﬃcult to explain the reasoning behind resource allocation to our non-physician collaborators or to a patient who succumbs to a ketoacidotic coma because his cheap insulin was not available. Considering the level of care used and accepted for patients with Ebola in Africa (no intensive care units needed, no very costly procedures, beds can be set up in tents, no expensive drugs), the low prices for protective clothing, the assumed full cooperation of African states, and almost negligible local salaries we do not understand the reasoning ourselves. The World Bank alone wants to spend more on Ebola than the entire health budget of Malawi—a budget that covers the cost of all the health challenges of 15 million people.3 Is the fear of the spread of Ebola really enough of an ethical reason to withhold eﬀorts and money from people suﬀering and dying not in projection, but in reality, from other diseases in Africa? We dare to doubt. We declare no competing interests. *Gregor Pollach, Christian Pietruck [email protected] Department of Anaesthesia and Intensive Care, University of Malawi, Blantyre, Malawi 1 Lewnard JA, Ndeﬀo Mbah ML, Alfaro-Murillo JA, et al. Dynamics and control of Ebola virus transmission in Montserrado, Liberia: a mathematical modelling analysis. Lancet Infect Dis 2014; 14: 1189–95. Queen Elizabeth Central Hospital. Annual reviews 2011–2014. Blantyre: Queen Elizabeth Central Hospital. Malawi Nyasa Times. Malawi budget statement 2013/2014. http://www.nyasatimes.com/2012/06/08/ malawi-budget-statement-for-20122013 (accessed Aug 22, 2014). 2 3 Ebola control: rapid diagnostic testing In their analysis of Ebola transmission,1 Joseph Lewnard and colleagues emphasise the need for an “acceleration of case ascertainment”, which so far has been a major challenge. Most patients with Ebola in west Africa remain undiagnosed in their communities, 2 and the average delay from symptom onset to diagnosis is about 5 days.3 For a PCR-based diagnosis, patients need to attend a laboratory, or visit a transit centre where blood can be drawn and transported to a laboratory. This process introduces delays during which Published Online November 19, 2014 http://dx.doi.org/10.1016/ S1473-3099(14)71035-7 100 Time to diagnosis 5 days 3 days 2 days 1 day 90 80 70 Attack rate (%) Harvard University Center for AIDS Research (P30 AI060354), and the Massachusetts General Hospital Executive Committee on Research. The content is solely my responsibility and does not represent the oﬃcial views of the National Institutes of Health or other funding agencies. I declare no competing interests. 60 50 40 30 20 10 0 0 10 20 30 40 50 60 70 80 90 100 Eﬀectiveness of isolation strategy (%) Figure: Proportion of the population eventually infected with Ebola according to eﬀectiveness of isolation strategy, by time to diagnosis 147 Correspondence See Online for appendix 148 transmission can occur. Accurate, point-of-care, rapid tests could minimise this window of transmission. If Ebola is diagnosed at home when symptoms first appear, household members could use protective kits until the infected person is securely transported to a treatment centre. To investigate the eﬀect of reducing the time between symptom onset and diagnosis with rapid testing, we used a standardised epidemic simulator4 for a population of 10 million and basic reproduction rate of 2·0. The proportion of the population eventually infected (attack rate) is shown as a function of the proportion of patients infected with Ebola who are diagnosed and then isolated (effectiveness of the isolation strategy; ﬁgure). If 60% of patients infected with Ebola are diagnosed rapidly and isolated, the attack rate drops from 80% to nearly 0% because the delay is reduced from 5 days to 1 day. Rapid point-of-care testing provides other advantages. Because Ebola causes common, non-specific symptoms, large numbers of people need to be tested in areas where most cases are unreported, such as Sierra Leone and Liberia. Establishing PCR capacity to meet this need remains a challenge. At the same time, transporting blood samples collected at remote sites is logistically diﬃcult and introduces contamination risks. Many patients are also reluctant to wait in so-called holding areas with others who might have Ebola for the several hours to days it takes for results, discouraging people from coming forward. Rapid testing could also prove useful for screening travellers at border crossings. Rapid diagnostic tests (RDTs) similar to those used for inﬂuenza and malaria are under development and might oﬀer a solution. In preliminary results from the Viral Hemorrhagic Fever Consortium, Ebola RDTs achieve greater than 90% sensitivity and nearly 100% specificity, similar to PCR. RDTs need only small quantities of blood obtainable by fingerstick, and could be applied safely by trained paramedical cadres. The large-scale introduction of rapid testing could reduce time to diagnosis and have a major effect on Ebola transmission. RFG has received grants from the National Institutes of Health, and is aﬃliated with the Viral Hemorrhagic Fever Consortium, which has developed diagnostic tests for Ebola, Lassa fever, and other viral diseases. All other authors declare no competing interests. *Ranu S Dhillon, Devabhaktuni Srikrishna, Robert F Garry, Gerardo Chowell [email protected] Brigham and Women’s Hospital, Boston, MA 02115, USA (RSD); Earth Institute, Columbia University, New York, NY, USA (RSD); Patient Knowhow, San Mateo, CA, USA (DS); Viral Hemorrhagic Fever Consortium and Tulane University, New Orleans, LA, USA (RFG); and Arizona State University, Tempe, AZ, USA (GC) 1 2 3 4 Lewnard JA, Ndeﬀo Mbah ML, Alfaro-Murillo JA, et al. Dynamics and control of Ebola virus transmission in Montserrado, Liberia: a mathematical modeling analysis. Lancet Infect Dis 2014; published online Oct 24. http://dx.doi.org/10.1016/S14733099(14)70995-8. Meltzer MI, Atkins CY, Santibanez S, et al. Estimating the future number of cases in the Ebola epidemic—Liberia and Sierra Leone, 2014–2015. MMWR Surveill Summ 2014; 63: 1–14. WHO Ebola Response Team. Ebola virus disease in West Africa—the ﬁrst 9 months of the epidemic and forward projections. N Engl J Med 2014; 371: 1481–95. Chowell G, Nishiura H. Transmission dynamics and control of Ebola virus disease (EVD): a review. BMC Med 2014; 12: 196. Modelling the eﬀect of early detection of Ebola Almost 20 000 cases of Ebola virus disease have been reported in west Africa.1 Estimates of the reproductive ratio of the outbreak2–5 suggest that about half of infectious contacts need to be prevented to control the epidemic. The international response in the aﬀected regions has focused mainly on establishing infrastructure that enhances local capabilities to improve contact surveillance, eﬀectively isolate infectious people, educate people on mode of transmission and risk, and provision of supportive treament.6 PCR can detect Ebola virus in both human beings and non-human primates in the pre-symptomatic stage,7,8 and consequently, the eﬀect of timely diagnosis of pre-symptomatic individuals should be assessed. We evaluated the potential eﬀect of early diagnosis of presymptomatic individuals in west Africa. We used a simple mathematical model calibrated to the transmission dynamics of Ebola virus in west Africa. The baseline model includes the eﬀects of contact tracing and eﬀective isolation of infectious individuals in health-care settings (appendix). In the absence of vaccines or eﬀective antiviral drugs for Ebola, controlling the outbreak relies on identiﬁcation of infectious people quickly enough to break chains of transmission. Several organisations have developed pointof-care Ebola diagnostic tests, which have been proposed for door-to-door screening campaigns and in contact tracing in west Africa.9 Nevertheless, tracing contacts has been hampered by the diﬃculty of keeping track of the many ongoing chains of infection. We found that the eﬀect of early diagnosis of pre-symptomatic infections is strongly dependent on the eﬀectiveness of isolation of infectious individuals in health-care settings. For instance, with an isolation eﬀectiveness of 50% and with an average time of 3 days from the onset of symptoms to isolation, the attack rate (total number of Ebola cases per population size) remains essentially unchanged as the rate of detection of pre-symptomatic cases increases (ﬁgure). By contrast, early detection of pre-symptomatic individuals can have a striking eﬀect on the transmission dynamics of Ebola if the eﬀectiveness of isolating infectious people is at least 60%. Even at this level of isolation, at least 50% of pre-symptomatic patients would need to be detected in the community, which is diﬃcult to achieve with limited resources. www.thelancet.com/infection Vol 15 February 2015