key: cord-0008165-wrpn15qf authors: Chowell, Gerardo; Viboud, Cécile title: Controlling Ebola: key role of Ebola treatment centres date: 2015-01-07 journal: Lancet Infect Dis DOI: 10.1016/s1473-3099(14)71086-2 sha: 7c89c012026962f49a6bfd00320f16a1e271235a doc_id: 8165 cord_uid: wrpn15qf nan What initially was perceived to be a self-limited outbreak of Ebola virus disease in a forested area of Guinea has become an unprecedented epidemic of international concern that continues to spread unabated in parts of west Africa. 1,2 A lack of public health infrastructure together with delays in virus detection and implementation of control interventions have contributed to the widespread transmission of Ebola virus disease in a region inexperienced with this disease. 3 As in previous international health crises, such as the severe acute respiratory syndrome epidemic and the 2009 infl uenza pandemic, mathematical models are proving instrumental to guide the public health response against Ebola virus disease and monitor the eff ectiveness of control interventions. 4, 5 Whereas earlier modelling eff orts have relied on compartmental homogeneous-mixing models, 6-8 the study by Stefano Merler and colleagues, 9 reported in The Lancet Infectious Diseases, uses a microsimulation model to capture spatial heterogeneity in the transmission dynamics of Ebola virus disease in Liberia. Indeed, local epidemics of Ebola virus disease seem to be asynchro nous and show slower than expected growth, a pattern probably driven by the geometry of the contact network or social behaviour changes. 10 The model of Merler and colleagues incorporates fi ne details of Liberia's population structure and geography, including location of households, hospitals, and Ebola treatment units. Infectiousness is assumed to intensify in the later and more severe stages of Ebola virus disease, when infectious individuals are confi ned at home or in the health-care setting, and exposed to a restricted number of caregivers. The resulting contact network is highly clustered, giving rise to a slow and local mode of dissemination, 9 a pattern that homogeneous-mixing models have been unable to capture. Long-distance transmission events (eg, during unsafe funerals) are predicted to be uncommon; instead, the slow geographic spread of Ebola virus disease is best explained by distance travelled to reach a hospital. 9 This point is interesting, because several long-distance transmission events were key in the dissemination of the infection to neighbouring countries (Mali, Nigeria, Senegal) and other continents (Europe [Spain], North America [USA]). 2 One important aspect of the model by Merler and colleagues is to assess the eff ectiveness of intervention measures put in place in Liberia since mid-August, 2014. 9 In the pre-intervention period from June to mid-August, 2014, most of the Ebola infections were estimated to occur in hospitals (38%), followed by households (31%), the community (22%), and at funerals (9%). The rapid establishment of new Ebola treatment units was a key step to curb the epidemic in Liberia, although the model assumes near perfect isolation of infectious individuals in Ebola treatment units, which could be overly optimistic. Distribution of household protection kits and implementation of safe burial procedures were also associated with signifi cant reduction in Ebola virus disease transmission. Of note, other interventions not explicitly modelled could have played a part, including use of rapid diagnostic kits in Ebola treatment units, which reduces the delay from presentation to isolation, and changes in population behaviour in response to mass education campaigns and accumulation of Ebola virus disease cases. 11 Some of these eff ects could have been absorbed in the model by Merler and colleagues 9 through the estimated eff ect of household protection kits. The model by Merler and colleagues provides a substantial improvement compared with earlier homogeneous mixing models [6] [7] [8] and in turn their more optimistic predictions align better with the observed trajectory of the epidemic in Liberia. 9 However, the model tends to underestimate Ebola treatment unit admissions and predicts an earlier peak than reported, suggesting that further improvements could be useful. Ideally, future models should integrate more realistic population mobility patterns derived from cellphone usage data (eg, fl owminder), proxies of social behaviour, and diff erences in reporting and hospitalisation rates between rural and urban areas. However, these important data are lacking for the region. The outlook for Liberia has substantially improved over the past few weeks with news of an epidemic slowdown 2 (fi gure). By contrast, incidence has remained relatively stable in Guinea, whereas the epidemic continues to ascend quickly in Sierra Leone (fi gure). Diffi culties in building and staffi ng Ebola treatment units could explain the worrisome turn of the outbreak in Sierra Leone. A key test of the robustness of the model by Merler and colleagues will be whether it can reproduce the highly distinct dynamics of Ebola virus disease in diff erent countries. In the longer run, In clinical trial settings the standard 6-month treatment regimen for drug-sensitive pulmonary tuberculosis can achieve relapse-free cure in more than 95% of people. However, poor adherence might increase the risk of relapse and lead to drug resistance. Shortening the duration of treatment has become a major priority for global control of tuberculosis-it will benefi t patients and reduce the selection pressures that lead to the evolution of new drug-resistant strains. 1, 2 Attempts to use shorter courses of standard regimen drugs have not been successful except for smearnegative disease, 3, 4 and recent research has focused on fl uoroquinolones. The authors of a Cochrane review of fi ve studies assessing 6-month fl uoroquinolonecontaining regimens to treat drug-sensitive disease concluded that the available evidence was of low quality: the only consistently reported clinical outcome was all-cause mortality. 5 However, data from studies of mice and phase 2 trials suggested that use of fl uoroquinolones could shorten treatment for drugsensitive tuberculosis from 6 months to 4 months. 6 This possibility has now been assessed in human beings in four large phase 3 randomised controlled trials. [7] [8] [9] [10] Although fl uoroquinolone-containing regimens led to more negative culture results at 2 months, this did not translate into improved clinical outcomes when treatment was shortened (fi gure). The RIFAQUIN, 7 OFLOTUB, 8 and REMoxTB 9 trials benefi tted from large numbers of patients, more than 18 months of follow-up, and robust methods (such as the ability to diff erentiate relapse from reinfection by strain typing). A trial done by the Indian National Institute for Research in Tuberculosis was discontinued early on account of an unacceptable number of relapses. 10 The non-inferior result of the RIFAQUIN 6-month group, in which high-dose rifapentine and moxifl oxacin were given once weekly in the continuation phase, seems consistent with fi ndings from previous trials of 6-months' treatment with fl uoroquinolones, suggesting that they are broadly equivalent to the standard regimen. Apart from the 6-month RIFAQUN once-weekly regimen, which could be useful in some settings, it is disappointing that, despite these large trials-each costing several million dollars and lasting up to 10 years-we remain with the same 6-month regimen used in the 1970s. Since fl uoroquinolones alone do not seem to allow treatment to be shortened, it is We declare no competing interests. EV and PJK were supported by the Gordon and Llura Gund Foundation, EV by the National Research Fund for Tick-Borne Diseases, and PJK by the National Institutes of Health Epidemiological, clinical, and laboratory characteristics of 48 cases with "Babesia venatorum" infection in China: a descriptive study Babesia venatorum infection in child Human babesiosis Human babesiosis, an emerging tick-borne disease in the People's Republic of China Detection of Babesia divergens using molecular methods in anemic patients in Shandong Province Babesiosis: recent insights into an ancient disease Babesiosis surveillance-18 states Transfusion-associated babesiosis in the United States: a description of cases The case: hemolysis and acute renal failure Increasing health burden of human babesiosis in endemic sites Babesiosis in Lower Hudson Valley Co-infections with Babesia microti and plasmodium parasites along the China-Myanmar border Genetic diversity of babesia in Ixodes persulcatus and small mammals from North Ural and West Siberia Transmission dynamics and control of severe acute respiratory syndrome Pandemic potential of a strain of infl uenza A (H1N1): early fi ndings Dynamics and control of Ebola virus transmission in Montserrado, Liberia: a mathematical modelling analysis Strategies for containing Ebola in west Africa Transmission dynamics and control of Ebola virus disease (EVD): a review Spatiotemporal spread of the 2014 outbreak of Ebola virus disease in Liberia and the eff ectiveness of nonpharmaceutical interventions: a computational modelling analysis The western Africa Ebola virus disease epidemic exhibits both global exponential and local polynomial growth rates Is West Africa approaching a catastrophic phase or is the 2014 Ebola epidemic slowing down? Diff erent models yield diff erent answers for Liberia UN Offi ce for the Coordination of Humanitarian Aff airs. The humanitarian data exchange-Ebola treatment centers or units (ETCs or ETUs)