Understanding the link between Zika Virus and Microcephaly (babies with small heads)

Baby with small head (microcephaly) born to a woman
infected with
Zika virus. Image credit to  CTV News

In the last few months, the world still recovering from the terror of the Ebola virus, has woken up to a new one in the shape of the Zika virus. And what makes this one a terrorist, unlike Ebola which kills its hosts and is very highly contagious, is the strongly emerging evidence of it being responsible for a condition called microcephaly in babies of mothers infected with the virus while they were pregnant (a medical condition in which babies are born with abnormally small heads) as the virus has been isolated from the umbilical cord of these babies and from their mothers' blood. Microcephaly results from either a small brain substance volume; the premature closure of the sutures of the skull bones, or defects in skull bone growth and development, all of which then limit the growth of the brain substance to below the normal size. While the cause of these problems leading to an abnormally small head is multi-factorial, ranging from hereditary genetic disorders to environmental players like inadequate intake of some vital supplements by the pregnant woman and exposure to radiation in pregnancy---it's very vital to work out, in the smallest of details, how the Zika virus has come to be a player and the various mechanisms with which it likely employs to achieve this mischievous feat.

Ebola virus and the Future of Containing very Highly Infectious Diseases.

The Ebola virus. Image credit to
the BBC

Now Africa is faced with a new threat in the form of the Ebola virus; the death toll is rising in the three African countries-Guinea, Liberia and Sierra Leone-where the outbreaks occcurred this year. The Ebola virus, part of the haemorrhagic fever viruses, is extremely contagious and has a fatality rate of about 90%, meaning that 9 out every 10 people with the infection will likely not survive; though the rate so far has been about 50% and 60%. First reported in 1976 along the Ebola River in Zaire (now the Democratic Republic of the Congo), there was no outbreak between 1980 and 1993; some outbreaks occurred in some years between 1994 and 2012; this year's outbreak is the worst since it was discovered in 1976.

And the dawning of this reality has evoked in me questions about how the world, especially Africa, will position itself to tackle future occurrences (probably not the Ebola virus, as it may be eradicated if we get all the necessary public health measures in place) of new viral diseases that may be far more infectious than Ebola and Lassa viral infections.

A few months back, a case of Lassa fever was reported in the Paediatrics department of our teaching hospital, the University College Hospital, Ibadan; we had what we call Grand Round, a weekly seminar on pressing health issues, where this Lassa fever case was discussed in full details: it was at this seminar that I learnt that the one-use, disposable protective suit won by the health personnel managing a patient with the disease costs about 20,000 naira (about $150) which majority of Nigerian patients, who by the way do not have health insurance, can't afford (as about 3 or 4 of this suit will be required daily by the health workers, who would take shifts, to manage the infected quarantined patient-that's between $450 and $600).

While the best option now in the current case of Ebola virus is to provide excellent public health measures (there is hope as the World Bank has pledged $200 million, in addition to the $100 million dollars the World Health Organization and the three affected African countries jointly committed, to fight the outbreak in the affected African countries, including Nigeria) such as various forms of isolation units in hospitals to manage cases of admitted patients who present with the flu-like symptoms that have been associated with the Ebola virus infection, and isolating and monitoring those who brought the patient to the hospital (the treatment centre should also have the constitutional licence to isolate and monitor the patient's family members who came into contact with him or her after the onset of the symptoms); this outbreak has bared the need to establish and fund a multidisciplinary medical research facility in Africa to, among many other research duties, have a department of Unknown Highly Infectious Diseases. This department will be staffed by African medical research experts in Africa and in the diaspora who will collaborate with renowned medical experts in top research institutions around the world to quickly get samples from patients with suspected infectious, but unknown, disease for analysis of the possible cause and the firm establishment of various transmission modes of such a disease; and also to begin search for potential therapeutic (including a cure) modalities based on the accumulated knowledge from the various experimental studies that would have been carried out on the viruses.

In addition, the question of the ancestry and evolution of that new infectious disease-causing agent must be answered. Though this is a more demanding task, success at it will give the medical world insight into how for instance the Ebola virus and Lassa fever virus evolved (underwent mutations) to acquire their infectivity and virulence (the capacity of the viruses to cause the disease in people after infecting them) if there was a time in the ancestry of the viruses when they were not infectious; or even if they were infectious right from their first generation-how have they adapted and improved on their infectivity and virulence? It will also help in making quicker decisions in terms of the best path to follow in designing a treatment protocol if a virus in the same family, or a new strain of the same virus emerges in the future to cause disease in humans. This is getting more demanding and would mean spending more time with the virus in the lab, right? There's a possibility of a test tube containing blood samples of the virus slipping and spilling on to the researcher handling it; there could be an accidental needle pricking while trying to inject experimental mice or rats with the virus (to study immune system response to the virus for possible vaccine development); and a researcher dare not casually leave the lab to take some snacks, without following long protocols involved in removing his or her protective suit, no matter how hungry he or she may be. Is there a way to totally avoid the possible unforeseen hazard of infection that these researchers face in the lab while maintaining the same quality and quantity of research they will be doing on these very highly Infectious disease-causing viruses? A way that will enable a researcher to easily have lunch during work? I guess the solutions are in the future; but the future, I believe, is already here with us. And this future is where the extra collaborators from the US, Japan and other countries with very advanced robotics technologies will come in.

The da Vinci Surgical System. Image credit to
Robot Surgery.

For over a decade now, robots have been designed and modified to carry out surgery both in the battlefield and in the operating theatre under full control of human surgeons who operate them remotely, giving rise to the concept of the term Robo-Surgeon. The most popular and widely used of these robo-surgery technologies is the da Vinci Surgical System developed by Intuitive Surgical in Sunnyvale, California. This Surgical System comprises of a surgeon's console (a room-like compartment where the human surgeon sits very comfortably, equipped with a high-performance 3-D vision camera and master control like video game pads), a patient operating table with four interactive robotic arms and a collection of surgical instruments called EndoWrist instruments. To carry out a major surgery, the surgeon sits in the console that is separated from the operating theatre in which the patient is lying on the operating table of the Surgical System, and through the high-performance 3-D vision camera system uses the master controls of the console to direct the robotic arms to carry out intricate surgical tasks with very high level of precision, leaving behind very minimal scar. This application of robotics in surgery can be replicated in the experimental studies of very highly infectious agents like the Ebola virus and other future viruses and bacteria.

A prototype of a robot that can be telecontrolled
remotely by a human operator. Image credit to
The Indian Express

The future I imagine here will have the robotic arms replaced by more human-looking robots (something more like a Humanic from the TV science fiction series, Extant), but whose entire functions (movements, vision and decisions in the lab) will be under the total control of the researchers in the consoles outside the high bio-security labs in which these infectious samples are kept. Hence, the researchers will not need to be in these high bio-security labs in person, only their virtual presence, but they will be able to carry out their research works as though they were still in the labs; and moreover these Robo-Scientists, as I would prefer to call them, will be equipped with digital note-recording system to enable the human scientists controlling them to document the protocols involved in the research, any findings and results in the course of the research, and easily share them immediately with other labs around the world doing the same emergency research. This will speed up the development of therapeutic agents as results emerge from the work and are re-confirmed by other labs doing the same work in the shortest possible time. One more advantage: no human will be exposed to the infectious agents, only the Robo-Scientists and who can easily be sterilized. Sounds like science fiction, right? But the future is already here. And as the hundreds of millions of dollars committed to fight the Ebola virus outbreak begin to do its job; as the resolutions of the emergency meeting, in Geneva Switzerland, by the global health experts of the  World Health Organization (click on the link for the resolutions of the meeting) on drafting new measures to tackle the Ebola outbreak, held between Wednesday and Thursday, are made known to the public--I strongly hope the medical and corporate worlds will share in this future I envision and begin to set in motions the wheels that will contain the emergence of very highly infectious diseases, such as Ebola, in the future.

Scientists Begin to Unlock Some of the Keys to Drug Resistance

World Health Organization meeting on Drug Resistance in Leprosy.
Image credit to National Leprosy Eradication Programme

Some time ago I talked about the threat that drug resistance by disease-causing microorganisms poses to mankind if nothing is done now to tackle it. A few days later, the World Health Organisation echoed the same warning and emphasized the need for urgent action in finding new and potent ways to thwart this potential (and what I call) global terrorist attack by these disease-causing microorganisms as they continue to challenge our God-given right to replenish, conquer and dominate the world (for the animal activists out there, don't misunderstand me: I'm not talking about total annihilation of all microorganisms because there are the good guys among them who are minding their own business--the normal flora of our environment--and who are not challenging our God-given rights).

One of the disease-microorganisms that has developed what I call smart resistance to drugs which previously dealt with it is the tuberculosis-causing organism called Mycobacterium tuberculosis. This microorganism has evolved into to variants now known as Multi-Drug Resistant (MDR) and Extensive Drug Resistant TB that is unaffected by most of the first-line and second-line anti-TB drugs, requiring combination of anti-TB drugs from more than one class before the patient's condition can see any improvement. This type of treatment, to be effective, may take up to one year or more, meaning more cost and more side effects of these drugs to the patient (and the patient will have to pay for other drugs needed to counter some of the side effects): this places a big burden on patients in parts of the world where TB is more likely to flourish: the poor populace of the world where access to health care is very limited. In addition to this problem, a case of a variant of a particular disease-causing bacterium resistant to all known potent antibiotics has been documented.

Crystal structure of the LptDE complex.
Image credit to Nature.

But rights (our God-given rights), I believe, come with the necessary provisions and weapons to defend and protect them. According to a research published in the journal Nature, scientists have unraveled the structure and mechanism with which a group of drug-resistant bacteria, termed gram-negative, build their exterior coating wall that, over generations of mutations, has become impermeable to most antibiotics and also able to conceal the bacteria from the attack of its host (human) immune system. Scientists used the Diamond Synchroton facility in Oxfordshire, Oxford, which produces intense X-rays about 10 billion times brighter than that the light from the sun, to study crystalline forms of the isolated protein samples from the exterior of these bacteria at the atomic level. The result was an atomic-scale revelation of the structure of a protein complex called LptDE, in the cell wall of the bacteria. The detailed information gathered was then used to create models to simulate how this protein complex assembles molecules called lipopolysaccharide in the bacteria cell wall from the inside of the organisms; it was also found that the final stages of this assembly could be attacked from the outside using new antibiotics to shatter the whole assembly process and leave the bacteria exposed without a covering and vulnerable to the environment--the host immune system attack. One more good news is that the protein complex LptDE has been found to be almost the same across a broad range of gram-negative bacteria that cause a large number of diseases such as meningitis, meaning that designing a class potent antibiotics against this key structure could be the master key to treating these diseases. The way forward now, according to experts, is to start exploring this great opportunity to design novel drugs that can inhibit the mechanism of the protein complex, LptDE.

Diamond Light Source of the Synchroton Facility in Oxfordshire, Oxford.
Image credit to Diamond UK.

While this is a great basic and fundamental discovery and has brought much to hope for, isn't there a possibility that sustained offense against the LptDE mechanism (when we develop antibiotics against it) can trigger the need for these bacteria to undergo mutations that will alter some parts of the structure of the component proteins involved in the assembly work to render the designed antibiotics useless? There was a time when our current antibiotics were working wonders because they targeted what were found then as structures and mechanisms crucial to these microorganisms' survival; but the same crucial targets have become smart at adapting to our offenses.

Simulated model of the Lipopolysaccharide Assembly.
Image credit to Nature.

My point is that we've got to have many potent options (like I said in a similar post) at dealing with these microscopic bad guys. In addition to leveraging on this current discovery, and also embarking on a suggestion I made in a similar post, I believe there may be special areas in these microorganisms that are very vital to their survival and at the same time do not undergo mutations at the genetic level because any alterations in the molecular structure of these vital areas would destabilize the microorganisms. Efforts should be geared towards identifying these areas in the global MutaGenome Project-areas I will want to tag Rigidity Importance Sites in drug-resistant microorganisms because they are very important to their survival but do not undergo mutations no matter the changes in the organisms' environment. This will enable the development of drugs targeted towards the translational outcomes (protein structure) of these Rigidity Importance Sites (RIS) in the DNA of the microorganisms. And one way to do this could be by creating models of the genome of some of these microorganisms and try to simulate their genomic replication, transcription and translation using data gathered from accumulated laboratory investigations and all possible effects of environmental changes on their genome over several generations--this I believe may reveal these areas of the genome that hardly undergo mutations, irrespective of the extent of external threats, but are very very crucial to their survival. Drugs designed against these Rigidity Importance Sites will be extremely potent at eradicating these disease-causing niggers, and any attempt to develop resistance to the drugs by mutations will be fatally detrimental to them; hence, we have a double-edged sword against them.

And we'll keep on exercising our God-given fundamental rights to dominate over disease-causing microorganisms because there is hope and we are smarter than they are.