Ebola, lessons from an emerging viral haemorrhagic infection in a failing public health infrastructure

Ebola virus has all the elements required for an emerging infectious disease with epidemic potential: a zoonotic bat virus, high host plasticity, and a receptive ecological and ‘socio-political landscape’.[1,2,3] During recent times, the Zaire Ebola virus, carried by its presumed fruit bat reservoir, has covered thousands of miles across Central Africa to end up in the Guinea forest region.[4] Systematic deforestation, poverty-driven game hunting, neglected and collapsed health care systems, distrust in an inefficient and poorly resourced government response, and fluid borders with migrating people displaced in a war-torn region have fuelled the outbreak which spread with unprecedented speed.[3] Population growth, increased urbanization, and better mobility and connectivity further had a profound impact on the dispersion of Ebola cases. Within a few months, the outbreak had reached the capital Conakry and the neighbouring countries of Sierra Leone, Liberia, Nigeria, Senegal, and Mali.

In fact, we were lucky. Thanks to the clever and prompt application of the polio eradication infrastructure to contain the outbreak in Lagos and Port Harcourt, the Nigerian authorities were able to avert a truly apocalyptic scenario of Ebola virus disease ravaging Lagos and its 21 million inhabitants in July 2014.[5] The 2014 Ebola outbreak has demonstrated at least two things: 1) outbreaks like these are very likely to occur again, and 2) there is a pressing need to build resilient public health systems in the weakest countries if we want to halt future infectious health security threats.

The aim of this contribution is to assess the risk of spill-over of Ebola virus, to describe the clinical lessons learned from the current Ebola outbreak, to address the problem of persistence on future transmission, and to review how well the world is prepared for the next epidemic.

The zoonotic niche of Ebola virus

The mapping of the zoonotic niche of Ebola virus, based on reported Ebola outbreaks in humans and Ebola infections in animals, has identified moist tropical forests across 22 countries of West and Central Africa as the predicted suitable environment for zoonotic transmission of Ebola virus.[6] Twenty-two million people are estimated to live in these mostly rural areas. The Democratic Republic of Congo, Guinea, Uganda, Nigeria, Cameroon and Central African Republic belong to the top 10 countries where the population is most at risk.[7] The rapidly increasing human population in these areas and reliance on bush meat for protein may further accelerate the risk of spill-over of zoonotic viruses.[7] In addition, the increased international connectivity by air travel, often within the sub-Saharan African region, carries the potential for international spread, especially to countries with weak health care systems. During the outbreak, 60% of the travellers departing from Guinea, Liberia and Sierra Leone were estimated to be travelling to countries with inadequate medical and public health infrastructure.[8] One of the key messages in a Lancet paper on Global Health Security was, ‘The epidemic has shown that we are only as safe as the most fragile states and it is a reminder that improvement of the capacity of every country to find, stop, and prevent health threats is both in the world’s self-interest, and a moral imperative’.[9]

Clinical characteristics and case definition

Already early on in the outbreak, it became clear that haemorrhage was a late and uncommon although unfavourable sign, presenting in only 18% of the patients.[10] In contrast, gastrointestinal symptoms were frequent and could be life threatening.[11] Therefore, the name of the disease was changed from Ebola haemorrhagic fever to Ebola virus disease (EVD). The most commonly reported symptoms at presentation are fever, intense fatigue, loss of appetite, vomiting, headache and abdominal pain.[10,12] Unfortunately, these clinical features are too unspecific to discriminate infected from non-infected individuals. For example, in a retrospective cohort study in Sierra Leone, presentation with three or more symptoms like intense fatigue, confusion, conjunctivitis, hiccups, vomiting or diarrhoea increased the odds of EVD by 3.2 (95% CI, 2.3 – 4.4).[12] However, the sensitivity and specificity for identification of clinical cases was only 57.8% and 70.8%, respectively. In addition, there is an intense debate about fever as a criterion of the case definition. Around 13% of patients did not present with fever.[10,12] Similar observations were made by local physicians (personal communication). Non-reported over-the-counter use of antipyretics may be one explanation. In addition, non-contact infrared thermometers (NCIT) often perform poorly. In a review on the accuracy of hand-held devices to detect fever by scanning the forehead, inner eye corner or auricular meatus, the sensitivity and specificity ranged from 82% – 89% and 75% – 99%, respectively.[13] These studies suggest that the risk of missing febrile individuals (100% minus sensitivity) would be between 11% and 18%. Excessive perspiration and surrounding ventilation systems may have a cooling effect, further compromising the performance of NCIT as a screening tool for fever. Therefore, a high level of suspicion and rapid point-of-care laboratory diagnosis remain essential not to miss patients with EVD.

On December 29, 2015, Liberia, Sierra Leone and Guinea had successfully interrupted human-to-human transmission linked to the original outbreak, which started two years earlier. Up to then, over 28,000 cases had been reported[14], with an estimated 17,000 survivors, of whom 6,869 are officially registered. Apart from the psychological trauma of having survived a deadly disease in frightening circumstances in a treatment unit, survivors suffer from stigma, and social disruption because of loss of family and friends to Ebola. In addition, according to a systematic survey in a Sierra Leone EVD survivor care clinic, during the first five months after discharge, 76% of the survivors suffers from arthralgia, 24% from auditory symptoms such as tinnitus or hearing loss, and 60% from eye complaints.[15] Eighteen percent of the survivors developed at times sight-threatening uveitis, possibly because of viral persistence in the ocular chamber. Ebola virus can also persist in the central nervous system and cause encephalitis even after clearance of the virus from the blood.[16] These findings underscore the need for clinical follow-up and care of all survivors and emphasize the need to strengthen universal access to ocular care.

Ebola virus can also persist in semen and has been linked to sexual transmission of Ebola virus in Liberia after the outbreak had ended.[17] It is not yet known how long semen remains infectious, although viral RNA has been found up to nine months after the onset of EVD.[18] Transmission through sexual contact is a rare event, but it may be responsible for late EVD cases, well past the incubation period of 21 days. It is therefore of paramount importance to include the sexual history in the medical evaluation of patients returning with fever from former Ebola epidemic regions.

To effectively manage the residual risk of re-emergence of EVD from reservoirs of viral persistence, the WHO has designed a phase-3 Ebola response framework.[14] This framework consists of 3 pillars: 1) expanding the network of clinical services to all survivors and offering voluntary semen screening and counselling programs for male survivors to protect close contacts (PREVENT); 2) implementing a nationwide surveillance strategy to screen all living or deceased individuals with symptoms compatible with EVD (DETECT); 3) deploying rapid-response teams following detection of a new confirmed case (RESPOND). Progress in the key performance indicators by the different countries can be followed on the WHO Ebola situation report website.

Need for major reforms

Every outbreak with pandemic potential is a game-changer in how the world prepares for the next serious epidemic. Outbreaks like SARS and pandemic H1N1 identified weaknesses within our ability to address global health emergencies and resulted in new approaches such as the revised International Health Regulations (IHR, 2005) and the Pandemic Influenza Preparedness Framework (PIPF, 2011). However, most countries failed to meet the 2012 deadline for fulfilling the obligations on national surveillance and rapid response capacities as stipulated in the IHR. Especially, low-income countries in the epidemic hot zone like Guinea, Liberia and Sierra Leone lacked infrastructure, strategy and funding to comply with the IHR obligations.[9]

In the Ebola outbreak, there were failures at almost every level. Therefore, major reforms and recommendations have been formulated by independent bodies such as the Independent Panel on the Global Response to Ebola and the Commission on a Global Health Risk Framework for the Future.[18,19] Taken together, these recommendations revolve around four themes. First, ‘All countries need a minimum level of core capacity to detect, report, and respond rapidly to outbreaks’.[18] However, it needs to be stressed that it is equally important to include promotion of individual access to safe and effective health services, products and technologies aimed at gaining public trust, and securing community engagement.[9] Second, the WHO needs ‘to meet its responsibility for responding to major disease outbreaks and to alert the global community’.[18] Third, ‘Rapid knowledge production and dissemination are essential for outbreak prevention and response’.[18] And finally, ‘An effective worldwide response needs leadership, clarity about roles and responsibilities, and robust measures of accountability’.[18] The recommendations will substantially reform existing bodies and create new processes and financial arrangements. Hopefully, we will act now ‘before the opportunity is lost as global attention moves on’.[5] The next serious outbreak will be as unexpected as Ebola, and it will thrive on our failure to implement the lessons we have learned from the past.

References

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