Recent infectious disease epidemics illustrate how health systems failures anywhere can create disease vulnerabilities everywhere. We must therefore prioritize investments in health care infrastructure in outbreak-prone regions of the world. We describe how “rooted” research collaborations can establish capacity for pathogen surveillance and facilitate rapid outbreak responses.

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Heymann et al., 2016 Heymann D.L.

Liu J.

Lillywhite L. International research collaborations are essential in combating major public health emergencies. Failure to collaborate can delay critical findings, hamper outbreak response, and erode trust between institutions and nations. In this commentary, we expand on recent discussions on the lack of openness during public health emergencies and perceived exploitation of disease-stricken countries by “parachute researchers” (). We draw on our experience establishing the Viral Hemorrhagic Fever Consortium and the African Center of Excellence for Genomics of Infectious Disease in West Africa and show how “rooted” collaborations can assist during public health emergencies. Recognizing that many successful infectious disease research collaborations exist, we highlight their critical and often unheralded role in mitigating and preventing infectious disease outbreaks.

Infectious disease outbreaks continue to pose challenges to global health and security, prompting reactive countermeasures. Recently, severe outbreaks of Ebola and Zika virus were designated by the World Health Organization as “Public Health Emergencies of International Concern.” Other emerging viral pathogens have warranted similar attention, including virus outbreaks from Lassa, Chikungunya, avian influenza, Nipah, SARS, and MERS. Additionally, endemic human pathogens, such as dengue and West Nile virus, have expanded to new regions due to changing demographics and increased urbanization.

UNESCO, 2015 UNESCO (2015). UNESCO Science Report: Towards 2030. http://en.unesco.org/unesco_science_report. Marsh, 2016 Marsh, K. (2016). How Africa can close its continent-wide science funding gap. Marsh, 2016 Marsh, K. (2016). How Africa can close its continent-wide science funding gap. Due in part to underinvestment in health care infrastructure and scientific research, Africa harbors a disproportionate infectious disease burden and vulnerability to acute outbreaks. Though more than a billion people call Africa home, the continent produces only 5% of the world’s gross domestic product (). Total investments in African research and development (R&D) rose more than 50% between 2007 and 2013, but still comprise less than 1.5% of the world’s total R&D expenditure (). This increase in investment, however, translated into an immediate expansion of scientific output, with a rise in publications of 60% from 2007 to 2013, compared to less than 15% in Europe over the same period ().

Health care and disease surveillance disparities can exacerbate local outbreaks into global infectious threats. The large imbalance between health care capacity in Africa and most western nations means that serious infectious disease outbreaks in Africa should be shared concerns in the US, Europe, and elsewhere. Controlling pathogens that lack effective vaccines and therapeutics make early detection, isolation, and contact tracing critical. However, even when effective vaccines are available—such as in the recent outbreaks of yellow fever in Africa and measles in the US—breakdown of health care infrastructure and/or low vaccination rates allow preventable infectious diseases to spread. Combined with an ever expanding human population and an increase in the ease of travel, infectious disease outbreaks can therefore no longer be considered local threats, but rather represent international emergencies. With these factors in mind, we anticipate recurring interactions with severe pathogens, with unpredictable consequences to human health.

Rooted Research The recent Ebola and Zika epidemics illustrate how vulnerable the world can be to the threat from severe viruses. To effectively combat such pathogens, the global community must prioritize investments in health care infrastructure in regions of the world most susceptible to outbreaks, and establish local capacity for pathogen detection and containment before they occur. This capacity building should not only focus on the potential danger from emerging pathogens, but rather should address ongoing matters of local public health importance. Well-established research collaborations are at the center of creating such capacity and can serve as a major source of knowledge transfer and preparedness before, during, and after an outbreak. This is a much more powerful and cost effective strategy than reacting once the outbreak has begun, as in the 2013-2016 Ebola virus disease (EVD) epidemic. Baize et al., 2014 Baize S.

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et al. What would become the largest recorded EVD outbreak began in December 2013 in Guinea, yet was not detected until March 2014 (). Local outbreak responders contributed vital efforts during the epidemic—tragically resulting in more than 500 deaths of West African healthcare workers (). Ultimately, more than USD $7 billion were raised for the response, but despite this large injection of foreign capital, only once the local response was sufficiently strengthened did the region control the outbreak. Collaborative clinical research played a key role in facilitating this, by ensuring comprehensive training of West African outbreak responders. In addition, some of the diagnostic and surveillance laboratories established during the epidemic remain in place and continue to support case investigations by local researchers (). These operations added critical capacity to detect and investigate the multiple flare-ups of EVD observed over the last year and continue to be instrumental in determining likely transmission chains originating from EVD survivors (). Heymann et al., 2016 Heymann D.L.

Liu J.

Lillywhite L. Heymann et al., 2016 Heymann D.L.

Liu J.

Lillywhite L. Heymann et al., 2016 Heymann D.L.

Liu J.

Lillywhite L. Despite the ultimate containment of EVD, however, collaborations during the 2013–2016 EVD epidemic—like many other public health emergencies before it—were often sub-optimal (). In some instances, researchers “parachuted” into the affected countries, conducted research in isolation, and departed without creating sustainable infrastructure or a lasting impact. In several cases, international scientists with no established collaborations in West Africa allegedly transported samples back to their home countries for further research, in many cases without permission or knowledge of the affected nations (). Parachute research can be detrimental to emergency response by preventing sharing of resources critical to public health and fails to enhance the capacity of affected regions to combat future outbreaks (). Figure 1 Pillars Underlying Rooted Infectious Disease Research Collaborations Show full caption Rooted partnerships operating during public health emergencies are commonly built on four pillars—co-creation, capacity building, sustainability, and openness—that enable immediate and long-term approaches for outbreak response. Artwork by Sigrid Knemeyer. A more successful and sustainable approach to outbreak response is built on collaborations that incorporate both immediate and long-term solutions for outbreak prevention into their infectious disease research programs. We term this “rooted research” to reflect the need for securing the research with a firm foundation in the affected countries. As opposed to parachute research, rooted partnerships operating during public health emergencies are commonly built on four pillars: (1) co-creation, (2) capacity building, (3) sustainability, and (4) openness. Co-creation, through the mutual agreement on research goals, outcomes, and scientific publications among partners. Capacity building, through frequent training and establishment of scientific infrastructure. Sustainability, by providing short-term and long-term research goals, and continued technology transfer among partners. And finally, openness, by immediate public sharing of data, analyses, findings, and, if feasible, resources and samples ( Figure 1 ). We are not advocating simply for the creation of additional research consortia or recognition of the general benefits of scientific collaboration. Research collaborations have become standard practice across all sciences; addressing big scientific challenges, such as emerging infectious disease surveillance and control, unquestionably requires large, multi-disciplinary teams. We also recognize that one size does not fit all for research collaborations and that there exist many successful approaches to forming lasting and mutually beneficial research partnerships. Rather, we seek to highlight the critical and often unheralded role of rooted research collaborations in mitigating and preventing infectious disease outbreaks. Sustainable partnerships build trust and capacity upon which outbreak responses can be quickly mobilized.

Collaboration, Education, and Capacity Building in West Africa Our collective experience establishing research consortia in West Africa—one among many infectious disease collaborations—provides insights into the value of rooted research partnerships. We have tried to build and guide these collaborations adhering to the four pillars of co-creation, capacity building, sustainability, and openness. Building on decades of research experience in West Africa, we—researchers from West Africa and the US—co-created the Viral Hemorrhagic Fever Consortium (VHFC; www.vhfc.org ) in 2010 with the goal of enabling research leading to better diagnostics and treatments for Lassa fever—a virus that causes hemorrhagic fever in thousands of people annually. The VHFC unites the world’s only two Lassa fever wards, at Kenema Government Hospital (KGH), Sierra Leone, and Irrua Specialist Teaching Hospital (ISTH), Nigeria, with academic, government, and industry partners. Investment by local ministries of health and US governmental agencies has supported clinical centers capable of reliable diagnosis, clinical care, and investigation of category-A level pathogens in otherwise austere circumstances. Together, in 2014 we also founded the African Center of Excellence for Genomics of Infectious Disease (ACEGID; acegid.org ), centered at Redeemer’s University, Nigeria with support from the World Bank and H3Africa. ACEGID expands infectious disease research and training among West African researchers and has established genomic sequencing capabilities for the study and surveillance of human pathogens. Capacity building and long-term sustainability have both been central tenets of ACEGID and VHFC. In addition to investment in clinical, diagnostic, and research infrastructure, both consortia also have a significant focus on training African researchers, combined with frequent technology transfer to West Africa. By creating ACEGID we sought to expand the training part of our collaborations, by creating long-term graduate-level (M.S. and Ph.D.) programs for African university students, as well as short-term foundational training programs for African educators and laboratory technicians. In addition to training at host institutions in West Africa, we have established two-month training programs for African educators and researchers hosted each year in the US. Now entering its third year, this annual program has educated over two dozen students in a training-of-trainers model, covering molecular diagnostics, microbiology, evolutionary genetics, and teaching pedagogy. Ultimately, we aim to modularize and extend this approach, pairing laboratory enhancements and education to create a critical mass of well-trained African scientists to carry out genomic infectious disease surveillance in West Africa. Gire et al., 2014 Gire S.K.

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et al. The establishment of VHFC and ACEGID facilitated rooted collaborations that not only allowed us to perform research on Lassa fever directly in the communities most affected by them, but to be better prepared for the emergence of another viral hemorrhagic fever virus. As the EVD epidemic spread to Sierra Leone and then Nigeria, the research capacity and partnerships developed in-country enabled early and critical response and insights into the outbreak. Within a week after Ebola virus was confirmed in Guinea, together with the Sierra Leone Ministry of Health and Sanitation, we implemented PCR-based diagnostic tests for Ebola virus at KGH to supplement already available diagnostic assays for other severe pathogens. This enabled local staff to rapidly detect and respond to the first Sierra Leonean EVD patient who presented at KGH at the end of May 2014 (). The same tests were introduced at Redeemer’s University, which allowed Nigerian researchers to quickly diagnose the first case of EVD in Nigeria in July 2014. Over the ensuing months, Sierra Leonean and Nigerian researchers continued to play a critical role in diagnosing EVD cases and other febrile patients. Schieffelin et al., 2014 Schieffelin J.S.

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et al. In addition to these diagnostic efforts, our collaborations also made possible several scientific studies that could be shared rapidly and openly to ensure maximum utility from the research. Open sharing of data and analyses encourages close collaborations, enables broad investigations, and can help correct or corroborate analyses that the original investigators had posited. Our efforts allowed us to investigate clinical features of EVD () and dissect the molecular evolution and spread of Ebola virus during the epidemic (). We immediately released all the generated data into the public domain - a practice many other groups also followed during the epidemic. The rooted collaborations in Sierra Leone and Nigeria also led to the development and manufacturing of an Ebola virus rapid bedside diagnostic test (Corgenix ReEBOV), co-created by Sierra Leonean and American partners. A similar assay had previously been developed for Lassa virus; both tests were used in Sierra Leone during the epidemic, and via new collaborations are now expanding their reach into other West African countries. Notably, much of the research was performed and directed by West African researchers with shared co-first and co-senior authorships on the resulting scientific publications. We believe these advances would have been delayed or impossible were it not for existing commitments to long-term rooted scientific projects in Sierra Leone and Nigeria.