Dr. Francisco Javier Carod Artal

Director of the Máster en Neurología Tropical y Enfermedades Infecciosas. Consultant Neurologist at the Department of Neurology in the Raigmore Hospital. Inverness, United Kingdom.

Q. The Ebola and Zika epidemics are the focus of much attention of late. Do you think that the severity of these epidemics really makes them worthy of such media coverage?
A. In the last 25 years there have been a number of epidemics of different viral diseases in tropical regions. Some of them did not have so much impact in the media, as is the case of the dengue epidemics that devastated South America a couple of decades ago.
Perhaps, now, the impact of the recent epidemics of Ebola virus and Zika virus have come to the public's attention as a result of the high rate of mortality due to the Ebola virus and of the cases of microcephaly and Guillain-Barré syndrome associated with the Zika virus.
If we analyse the latest epidemics of emerging viral diseases that have occurred over the last few years, it can be seen that many of them have been transmitted by insect vectors. Infections due to dengue, west Nile and chikungunya viruses reached epidemic proportions in different areas of the world and affected hundreds of thousands of people, although they had less impact in the media.

Q. To what extent can it be said that the Ebola epidemic is no longer a threat?
A. The epidemic appears to be under control at present. Yet there is still the risk of the appearance of new cases of the disease caused by the Ebola virus. There are a series of potential factors that could hypothetically favour the presence of outbreaks restricted to endemic geographical areas. Some of the most notable of these factors include a new lost chain of contagion, the reintroduction of the virus from an unknown animal reservoir, importation from an area where there is an active transmission of the virus or perhaps the reactivation of the virus that has persisted in a survivor. The last epidemic due to Ebola virus, which affected western Africa, is unique, because it is the greatest epidemic outbreak caused by Ebola virus, with over 28,600 cases and 11,000 deaths. Nevertheless, while there is just one single case that has not been diagnosed, there will remain a risk of a new outbreak. For example, Sierra Leona reported the end of person-to-person transmission in November 2015. As of that moment, the country entered a phase of active surveillance in order to detect sporadic cases. Two months after declaring the end of the outbreak, however, a new case of disease due to the Ebola virus was confirmed in January 2016 in a patient who died. In the days that followed, one of the relatives at risk, who was under active surveillance in quarantine, also developed symptoms of the disease. Fortunately, at the beginning of February 2016, this patient was discharged after confirming, for the second time, that no sign of viral RNA was found in a new blood sample. The situation in the other sub-Saharan countries affected can be summed up in one sentence: there is a need for active surveillance to detect any new case of suspected disease due to Ebola virus as quickly as possible.

Q. How likely are these epidemics to start up again because of variants?
A. The key issue in the case of the Zika virus is to understand why a virus that was self-limited to areas of Central Africa spread to Asia and Polynesia and, later, went on to America, causing an important epidemic outbreak. Perhaps the main source of concern lies in the insect vector. Aedes aegypti is the insect vector of the Zika virus, but also of the dengue and chikungunya viruses. This insect is capable of transmitting these arboviruses in densely populated suburban regions and in the outskirts of the large cities in South America, Asia and other tropical and sub-tropical regions. It is a mosquito that has adapted itself to human settings and even lays its eggs in water receptacles inside households. Nevertheless, problems of health standards and deficiency in the control of the population of mosquitoes have favoured the reproduction and multiplication of this vector. Moreover, the arboviruses that we have mentioned earlier, Zika, dengue and chikungunya, have adapted themselves to a very efficient human being-mosquito-human being cycle of transmission which, in tropical areas, favours its dispersion and spreading to other areas.
We still do not have enough data to know whether new, more aggressive, variants of Zika can appear (80% of those infected do not present any symptoms). The truth is that the phylogenetic studies conducted with the Zika virus show a number of variations in its structural proteins, but we do not know if this implies a more efficient adaptation of the virus to a new setting, a more pronounced neurotropism, or even whether these variants that have been observed have any pathogenic value.
Further studies are also needed to comprehend the origin of the degree of neurovirulence and potential neuro-invasiveness of the Zika virus in the central nervous system.
With respect to the dengue virus, we know that the risk of suffering haemorrhagic dengue is greater in people who have previously been infected by dengue virus. It is not known whether this can also occur with the Zika virus. Likewise, we have known for some time now that infection due to the dengue virus is associated with a range of different immune-mediated neurological syndromes such as Guillain-Barré, transverse myelitis, acute disseminated encephalomyelitis and paralysis of the cranial nerves. Our experience with Zika virus goes back only 60 years and perhaps the neurological complications associated with infection by Zika have been under-diagnosed.

Q. Some opinions published in reputable specialised media have defended the idea that these epidemics must be considered a warning so that steps are taken to reinforce preventive measures – do you agree?
A. The public health policies in tropical countries should be focused on fighting the insect vectors that transmit the arboviruses and on improving the systems of early detection, diagnosis and treatment of the complications associated to the infections they give rise to. But there are a number of social, socio-economic and even cultural determining factors that can limit the efficacy of prevention, epidemiological surveillance and intervention programmes. Just think for a moment, for instance, of the difficulties involved in monitoring the disposal of detritus or controlling the presence of used tyres that fill up with water and make ideal containers for Aedes aegypti to lay their eggs in. Or also the ancestral practices involving the washing of the dead in Equatorial Africa, which puts people at risk of contagion by Ebola virus.
Other researchers think that climatic factors could be behind the successive viral epidemics transmitted by insect vectors. Nevertheless, we should not forget the unknown or potential reservoirs. Many arboviruses have adapted themselves to other mammals. Remember the case of the Japanese encephalitis virus in pigs. Hence the importance of entomological surveillance and reservoir research programmes. In short, there is a need to reinforce and reconsider the prevention programmes on a global scale, both in developing and developed countries.

Q. Could we say that the containing walls have weakened or that they are simply insufficient?
A. Both are true. But I believe that, in addition, there are a number of political, economic, social and climatic factors, amongst others, that can exert an influence, at any given time, on the genesis of an epidemic in the tropics. Containing walls are by definition limited and cannot stop new viruses and new infectious diseases spreading in this global village, although, of course, political will can help and favour containment systems.

Q. Do you think that national governments often fail to pay enough attention to WHO guidelines? Should there be an effective worldwide government to deal with health issues, at least as far as transmittable diseases are concerned?
A. The WHO is working actively and in close collaboration with the health ministries of the countries involved. Brazil declared a state of public health emergency in 2015, after having detected an increase in the number of cases of microcephaly of more than 20 times the average incidence of the previous years. At present, the country is waging a real battle against the mosquito vector of the Zika virus. Colombia and Brazil, the United States Centers for Disease Control and the WHO/Pan American Health Organisation have drawn up different protocols and guidelines to help recognise and treat the main neurological complications associated to the Zika virus. It is true, however, that there are also very important political issues at stake, such as the impact on the Olympic Games in Rio in 2016 or the effect on women who are, or are likely to become, pregnant living in regions where active transmission of the virus occurs. Due to the size of the pandemic, it is clear that a more effective healthcare policy centre should be set up with a management of a more executive nature. The WHO can play a key role in the coordination of the epidemic, the definition and identification of the problem cases, the design of intervention, diagnosis and treatment protocols as well as in providing the different local governments and populations with expert-level advice.

Q. The WHO has asked you to sit on the committee that is to assess the neurological complications of the Zika virus. Can you tell us something about the mission of this committee?
A. On 1st February 2016, the World Health Organisation declared the current epidemic outbreak of the Zika virus in America a Public Health Emergency of International Concern. Since the year 2007, 39 countries have reported the circulation of the virus in their territories. Given the growing incidence of the number of cases of microcephaly, Guillain-Barré syndrome and other neurological syndromes within the context of the current epidemic of Zika virus, the WHO has set up an emergency committee of experts that will assess and draw up guidelines on the diagnosis and management of the neurological complications associated to this virus. The aim is to create a series of recommendations about the diagnosis and treatment of microcephaly and immune-mediated neurological syndromes as well as to review the care of pregnant women within the context of infection by Zika virus.

Q. Could you sum up the warning signs that would be useful to neurologists and primary care physicians faced with possible infection by Ebola or Zika viruses?
A. Today, a growing number of cases of Guillain-Barré syndrome have been reported following infection by the Zika virus. Brazil, Colombia, Venezuela and Surinam, in the present outbreak, and French Polynesia, in the outbreak in 2007, have reported a significant increase in the incidence of cases of Guillain-Barré syndrome. Given the growing number of people who can travel or return to endemic areas where there is active transmission of the virus, neurologists, primary care physicians and doctors working in A

Q. Do you think that doctors receive sufficient training to be able to detect and treat these pathologies? Would you propose any formulae aimed at achieving improvements?
A. I believe that the training given in topics concerning global health, tropical medicine and, in particular, tropical neurology is deficient as it stands today. In view of the growing impact of the new emerging infectious diseases, many of them with epidemic characteristics, I think it is necessary to enhance training in these matters. Besides, many of the emerging virus can affect the central nervous system and act as a significant source of disability. Both graduate and post-graduate programmes should include specific training subjects dealing with global health and with tropical neurology, as well as updated knowledge about the new emerging infectious diseases. Master's specialisation courses are a good tool that makes it possible to adapt and offset these curricular shortcomings and problems. Distance-learning systems have proved to be very useful in this respect and allow healthcare personnel interested in training in these areas the chance to pursue courses without physically attending classes. We must use globalisation, Internet access and the new tools available for the dissemination of knowledge to do away with educational and training isolation, and to stimulate pre- and post-graduate training in global health and tropical neurology at an international level.Prof. Juan Vicente

Sánchez-Andrés
Director asociado de Revista de Neurología
Departamento médico, Viguera eds.

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