Birth defects are defined as one of the leading causes of infant deaths in the United States. It is not easy to detect the problems at early stages, and some children are put under threat as soon as they are born. Many babies are born with some parts of the body missing, malformed, or damaged. The defects of a head are the most frequent cases. Microcephaly is a defect that may influence brain development. It is a clinical condition that is usually characterized by having a smaller-than-normal head with less than -2 of standard deviation (Woods & Basto, 2014). The peculiar feature of this defect is its dependence on many genetic and environmental factors at the same time. Children with microcephaly suffer from numerous developmental issues.
Clinical Signs and Symptoms
Microcephaly is a developmental pathology that has one primary sign that cannot be neglected the size of a childs head is significantly smaller than that of other childrens heads of the same age and sex (Liuzzi et al., 2016). The childs head should be measured and compared with the measurements given in specific charts. There are no special tests to determine this pathology before a baby is born. Sometimes, an ultrasound scan can be used to identify this problem in the third trimester. Additional microcephaly symptoms are hyperactivity, backward-sloping forehead, delays in speech and movement, difficulties incoordination, and facial distortions (Madhukark, Bhaysaheb, Babasaheb, Tukaram, & Balkrishna, 2016).
Epidemiology
Microcephaly is a rare condition in the United States. 2-12% per 10,000 of life birth includes the cases of microcephaly in the US, and 1:10,000 is the stated rate globally (Madhukark et al., 2016). There are specific groups of children that may be affected. Brazil is the country where a large number of cases of microcephaly occurred during the last several years. 3174 cases and 38 deaths were recorded in Brazil in 2015 (Madhukark et al., 2016). Certain congenital conditions may be the reason for the creation of an affected group. Children, whose mothers use alcohol or certain drugs before or during pregnancy, have infections like Zika virus or chickenpox, or are diagnosed with PKU (phenylketonuria), are exposed in the womb.
Etiology
Microcephaly can be genetic or caused by abnormal brain development. In some cases, this pathology may be the result of chromosomal abnormalities or the changes in genes that are hard to predict, observe, and treat (Liuzzi et al., 2016). Other known causes of microcephaly include a wrong function of centrosomes and the growth of the cerebral cortex. Infectious causes are the presence of such viruses as rubella, cytomegalovirus (CMV), and Zika (Liuzzi et al., 2016). The Zika virus has certain effects on the development of microcephaly in children. It may infect the fetus when a parent is exposed to the Zika virus and cause certain neurodevelopmental dysfunctions (Madhukark et al., 2016). The last cause has a direct correlation in the epidemiological data because it proves the chosen affected group that includes the children whose mothers have the Zika virus.
Affected Systems
The nervous system is the main system that is affected in patients with microcephaly (Liuzzi et al., 2016). This system is responsible for the transmission of nerve impulses through the body. When delays occur, homeostasis is developed, and new changes influence human development. Wrong brain work influences the work of the muscular system that is responsible for the skeletal muscles contractions (Woods & Basto, 2014). The endocrine system may be challenged because of hormone delays that participate in neural processes.
Normal vs. Abnormal Development
Brain tissue is affected by microcephaly. Not many children can survive with microcephaly caused by the presence of the Zika virus in the brain tissue. The brain is a central part of the nervous system. The development of the nervous system begins when the notochord turns ectoderm into a neuroectoderm that can be developed in a neural plate. The neural plate forms a neural groove that is lined by a neural fold on each side. The next stage in brain development is the formation of the neural tube. It is formed during the third week of gestation (Denny et al., 2013). By the end of gastrulation, two ridges form two neural folds that become one neural tube. The neural progenitor cells can be found between the ridges. Fusion o the neural folds is initiated at several places of the rostral-caudal axis (Stiles & Jernigan, 2010). After fusion, two continuous epithelial layers are formed. One is outer surface ectoderm, and another is a neural tube. Before the end of the fourth week of gestation, the caudal neuropore closes, and the neural tube is formed (Stiles & Jernigan, 2010). At the beginning of the neurulation process, the embryo is 3-5 mm long. At the end of the neural tubes formation, the size of the embryo is 27-31 mm.
Figure 1: Morphological Changes of the Embryo (Stiles & Jernigan, 2010)
In Figure 1, there are several pictures that can be used as the fate-map of normal development of the neural tube in the embryo. A the formation of the neural ridges, B the beginning of the neural tube formation, C the end of the neural tube formation. Microcephaly is the condition caused by unpredictable and uncontrollable neural stem cell proliferation during the embryonic development that may result in the death of neurons (Denny et al., 2013). The Zika virus, as the main contributor of microcephaly in fetuses, may infect an organism and kill the primary stem cells that have to be properly developed in the brain. The loss of any neuron leads other changes in heads size and the development of human brain functions.
Treatment
The main threat of microcephaly is that no definite treatment can be offered to children. It is impossible to reverse complications or enlarge the size of childs head. No direct treatment, but only alternative ideas should be discussed. The goal of any treatment is to manage childs condition and support them and their families by any possible means, including speech and physical developmental therapies and occupational therapies which strengthen childs abilities. Some medications and relaxing exercises can be offered to deal with hyperactivity if any.
Personal Interest
The fact that people cannot find out treatment for such pathology, it is interesting and challenging to observe the latest news and achievements on the chosen topic. The consideration of biological research and conferences can help to check on the latest changes and realize if microcephaly can be treated, and children can be saved. It is not fair that children should suffer from such birth defect as microcephaly, and it is necessary to do something to find the solution.
References
Denny, K.J., Jeanes, A., Fathe, K., Finnell, R.H., Taylor, S.M., & Woodruff, T.M. (2013). Neural tube defects, folate, and immune modulation. Birth Defect Research Part A: Clinical and Molecular Teratology, 97(9), 602-609.
Liuzzi, G., Puro, V., Vairo, F., Nicastri, E., Capobianchi, M.R., di Caro, A., & Ippolito, G. (2016). Zika virus and microcephaly: Is the correlation, causal or coincidental? New Microbiologica, 39(2), 83-85.
Madhukark, G.V., Bhaysaheb, D.K., Babasaheb, K.K., Tukaram, D.R., & Balkrishna, S.S. (2016). Zika virus infection: An overview. World Journal of Pharmacy and Pharmaceutical Science, 5(4), 2191-2204.
Stiles, J., & Jernigan, T.L. (2010). The basics of brain development. Neuropsychology Review, 20(4), 327-348.
Woods, C.G., & Basto, R. (2014). Microcephaly. Current Biology, 24(23), 1109-1111.
In this paper, the Alabama Department of Public Healths policy on the Zika virus, as well as the ethical approach in business, will be discussed.
Alabama Department of Public Healths Policy
As the first Zika virus case was confirmed in Alabama at the beginning of 2016, the Alabama Department of Public Health launched a campaign to educate and prevent the spread of the disease among Alabama citizens. Moreover, 345 submissions were received by the Alabama Department of Public Health from the citizens that wanted to be tested; 39 of these tests demonstrated positive result (Alabama Department of Public Health, 2016).
The ADPH also issued an advisory for pregnant women, as well as travelers, and provided webcasts and videos about the Zika virus for citizens of the state. The policymaking continued as the disease reached Alabama and first residents were confirmed with the virus. Alabama physicians were asked to contact the ADPH if any of their patients demonstrated symptoms of the disease.
All suspected cases were asked to be reported to Infectious Diseases & Outbreaks via the ADHP website. Specific submission forms were provided for residents who wanted to be tested for Zika or chikungunya and dengue viruses. Specimens for the tests could be dropped off at local departments and were later delivered to BCL.
The ADHP and Senior Services worked together on the education of residents about the Zika virus; coloring books that contained information about the virus were distributed to pre-kindergarten students, as well as more than 8.000 citizens of the state.
Information for clinicians was provided via the website in the form of PDF files. As of today, the ADHP accepts proposals from the residents on mosquito surveillance.
Sarahs Case
Business ethics in large enterprises do not forbid recommendations from employees, even if these recommendations concern their friends or family. Thus, Sarah will not break any rules if she decides to interview Jane. However, she should hand her written recommendation to the director of the company so that the interview process is transparent. It would be unethical if Sarah did not mention that Jane is her friend and decided to conduct the interview herself, without any mentions about their relationships.
As the company does not provide money to fund additional training for the other two applicants, and Jane is qualified for the position, it seems logical to interview Jane for the job. However, if it is possible, the director of the company should be present at the interview to ensure that Sara does not supervise her friend or interviews her incorrectly.
The most ethical approach here would be to conduct an interview with all three applicants and choose one of them depending on the results of the interview. Sarahs choice cannot be entirely ethical as it is limited by the budget of the company. The other two applicants can be more suitable for the position but only after specific training. However, it is impossible to train at least one of them due to the financial issues of the company. If the main aim of the company is to find a qualified employee for the position, it is reasonable to interview Jane but at the highest level of transparency.
The ethical approach can be both the best and the worst one depending on the context. However, the advantage of the ethical approach is that it tries to avoid conflict of interests and present all parties with equal opportunities or choices. Nevertheless, it also heavily depends on the situation.
Reference
Alabama Department of Public Health. (2016). Zika virus. Web.
There are many types of vectors that transmit disease between two hosts, generally can be divided into biological and mechanical transmission, however, Mosquito is the most common one that responsible of transmission of many deadliest diseases such as: Malaria, Dengue fever, Chikungunya and Zika. There are 3,500 types of mosquitoes, but research has confirmed that female mosquitoes are responsible for the transmission of diseases because they feed on human blood, unlike the male who feeds on the nectar of flowers.
Transmission of Vector Borne diseases:
The propagation of the bacterium depends on several factors that are similar to the nature of the bacterium and the carrier; the human movement and its susceptibility to the impact of the infection of the bacterium and finally the environment surrounding the bacterium.
The movement of people gives sufficient information about the nature of the spread of disease and the susceptibility of human exposure to germs.
Zika virus> transmission
There is growing evidence that Zika virus infection during the first and second trimester is associated with increased risk for central nervous system malformation of the foetus. The risk associated with infection during the third trimester is unknown. Therefore, Zika virus infection should be considered as a risk throughout the entire duration of pregnancy.
The presence of viable Zika virus in semen has been detected up to 24 days after onset of Zika virus infection symptoms. The longest interval reported between the onset of symptoms in a male and the subsequent onset of the disease thought to be due to sexual transmission in a female partner is 19 days.
All the currently reported sexual transmission events are linked to symptomatic index cases. There is no evidence of transmission by asymptomatic sexual partners.
Diseases that spread by mosquito
There are many types of vectors that transmit disease between two hosts, generally can be divided into biological and mechanical transmission, however, Mosquito is the most common one that responsible of transmission of many deadliest diseases such as: Malaria, Dengue fever, Chikungunya and Zika. There are 3,500 types of mosquitoes, but research has confirmed that female mosquitoes are responsible for the transmission of diseases because they feed on human blood, unlike the male who feeds on the nectar of flowers.
Malaria > transmission of Malaria.
Zika virus> transmission
Chikungunya: Spread to persons by Aedes aegypti and Aedes albopictus mosquitoes. Chikungunya virus is transmitted rarely from mother to infant around the time of birth.
Dengue fever
Yellow fever.
Factors influence the spread of vector borne disease:
Human movement and global trade
Human mobility is a major behavioural factor in many vector-borne disease systems because it affects vector exposure and hence the transmission of pathogens. Human movement transcends spatial and temporal scales with different effects on disease dynamics. Understanding movement will enable identification of important people and sites in the spread of pathogens such as dengue, which then may provide targets for surveillance, intervention, and enhanced disease prevention.
Climate change and global warming
Transmission of the vector depends on several environmental factors, such as temperature, humidity and wind movement. The impact of climate change and heat transfer on mosquito susceptibility to move more widely. the climate changes mosquito and tick vectors adapt to new environments, which lead to shifts in the spatial distribution, seasonality and incidence rates of disease-carrying mosquitoes and ticks as they move to different regions.
Climate change can form the rates of emerging disease by numerous processes including a direct effect on mosquito and tick vectors, and indirect effects on human vulnerability to emerging VBDs. For example, warmer temperatures principal to lengthier breeding seasons and greater hatch rates.
The role of mosquito population control
Many diseases that humanity faces today have no available treatment, therefore the main form of prevention from diseases such as malaria and lymphatic filariasis -that are transmitted by mosquitos- is vector control. It is thus important to understand the different non-insecticide-based strategies such as biocontrol strategies that target different species, as well as mosquito behavioural knowledge.
Synthetic insecticides have played a major role in the fight against mosquitos, however, it has its many downsides. For instance, Insecticides must be regulated in a way so as not to cause widespread resistance. In addition, if not used with caution its effects on the environment other living organisms can be detrimental. Furthermore, one of the worst properties of synthetic insecticides is its negative effects on human health. This has been widely fought using chemical and non-chemical methods such as covering most parts of the body in bright coloured clothes, sleeping under a mosquito net, the use of plant-borne molecules as well as applying mosquito repellents such as dimethyl phthalate and N,N-diethyl mendelic acid amide. The most used technique however has been the mosquito net, nonetheless, it only protects during the night. Moreover, insecticide treated bed nets however effective are also prone to resistance, specially pyrethroids which the most commonly used. However, it’s important to mention that bed nets played an important role in reducing infection prevalence of Plasmodium falciparum by 40% from 2000 to 2015 In sub-Saharan Africa.
Various biocontrol strategies have been developed to target different stages in the mosquito lifecycle. These strategies include the use of natural molecules to either kill the mosquito, alter its behaviour to improve mortality or increase the release of sterile mosquitos.
The use of botanicals and plant-based mosquitocidals and malaria drugs have been widely researched in the past 10 years, however a lot remains to be discovered in this area. More than 80 plants have been studied to develop effective nanomosquitocides. Most of these molecules are potent at a few parts per million against species such as anopheles and Culex.
Mosquito predators have as well been used to fight mosquitos at different stages of their lifecycle. Mosquito instars are fed upon by water bugs, amphibians, fish and larvae of other mosquito species. However, the use of mosquito predators has generally focused on the use of larvivorous fish that proved to prey on mosquito larvae in different habitats. Nonetheless, the introduction of larvivorous fish as a tool for biological control comes at an ecological cost as the fish can create a threat to native aqua fauna.
Bacillus thuringiensis var. israelensi (BTI) is a gram positive, spore forming bacteria that is currently used as a mosquito larvicidal in most European countries. BTI releases toxins and virulence factors and selectively kill larvae. It showed to be particularly effective against Ae. aegypti and Ae. Albopictus. In addition, the use of entomopathogenic fungi has also been advancing, these fungi typically release spores that penetrate the mosquito cuticle, intoxicate it and lead to its death. Obviously, they also have their downfalls, for instance, BTI is prone to resistance if used for longer term, and it’s quite demanding to apply it in urban environments. As for entomopathogenic fungi, further research needs to be done to determine viability, infectivity and persistence of spores in mosquito field environments.
Sterile Insect Technique is a tool used to produces sterile males of the species by treating them with chemoterlizing techniques or irradiation. The strategy aims at reducing population by either causing dominant lethal mutations in sperm and create chromosomal deviations. and has been successfully used to eradicate Cochliomyia hominivorax from North and Central America. However, there is an initial need to reduce the number of wild males before the release of sterile ones, which makes it a bit challenging for this method to be applied widely.
Genetic engineering has also been used for population suppression through the introduction of a self-limiting gene. This lethal gene can be supressed using tetracycline, which allows for rearing the species in facilities prior to their release. In addition, being species specific ensures target species aren’t affected by it in the long term as it only works on reducing populations in targeted areas. biotech company called Oxitec investigating a direct approach to a line of genetically modified Ades aegypti mosquitoes called OX513A to reduce the population number of mosquitos in the wild. Inserting two genes, Lethality gene and Fluorescent marker gene. These genes were inserted in genome of mosquito eggs. The lethality gene makes the mosquito dependent on antibiotic Tetracycline, which is fed to them in the lab, but it’s not available in the wild. The Fluorescent marker gene produces a protein that glows red when exposed to a light of a certain wavelength that tells the scientist which mosquito have the lethality gene. After the first genetically modified mosquito grew into adults scientist bred them into the lab. These mosquitos passed on the genetic modification to each generation giving rise to a colony of genetically modified mosquitoes all dependent on Tetracycline.
Moreover, the more information obtained about the mating ecology of mosquitos increases the ability to develop effective strategies for population reduction. For example, studying courtship can help releasing high quality males. It is worth mentioning that most studies in this area exclude courtship and mating rituals which can be extremely useful.
The role of mobile application in reporting and repelling mosquitoes
The use of mobile applications in the repelling of mosquitoes has spread widely in recent times, but there is no study to confirm the safety and efficiency of these applications. Looking at users’ reviews on YouTube and on the app site, there is a significant variation between those who claim that applications have driven mosquitoes, while others argue that the application is ineffective. This variation may depend on the type of mosquitoes and the surrounding environment or may depend on the type of mobile phone used so there must be lessons to know the differences. However, many company create mobile application allowing users to report about mosquitoes, for instance, a Brazilian company called Colab technologia created an application called “Sem Dengue” this allows the user to report mosquitoes and the possibility of taking and uploading images and linked to the geographical location and this reports goes to the local authorities to take a further action.
Crowdsourcing projects are used in several applications to develop and promote health, including diagnosis, nutrition, disease surveillance ,health education, and for disaster preparedness and response.
Was awarded the first place at the NetSquared Challenge in 2008. Google maps allowed users to view and zoom in on satellite images of Kenya in order to display the locations where incidents of violence had been reported, including photos and videos, with textual content providing more detailed information.
Zika virus mosquito-borne flavivirus is the focal point of a continuous pandemic and open wellness crisis. Recently limited to sporadic cases in Africa and Asia, the development of Zika infection in Brazil in 2015 proclaimed fast spread all through the Americas. Most Zika virus contaminations are portrayed by subclinical or moderate flu-like disease, serious appearances were depicted, which incorporate Guillain-Barre disorder in grown-ups and microcephaly in infants destined to tainted mothers. Neither a ground-breaking treatment nor an antibody is to be had for Zika virus; along these lines, the overall population wellbeing response in the primary claims to fame of halting contamination, specifically in pregnant ladies. Notwithstanding developing ability around this infection, questions keep on being in regards to the infection’s vectors and stores, pathogenesis, hereditary assortment, and capacity synergistic results of co-contamination with other circling infections. Those inquiries feature the need for research to upgrade observation, quiet administration, and open wellness mediation inside the present-day Zika virus plague.
Introduction
Zika virus (ZIKV) is a member of the virus circle of relatives Flaviviridae. Flaviviridae is a family of positive single-stranded enveloped RNA viruses that are found in arthropods of mosquitoes. Zika virus is spread generally by the bite of a contaminated Aedes species mosquito (Ae. aegypti and Ae. albopictus). If infected while pregnant, a mother can pass the Zika virus to her unborn child. Zika infection during pregnancy can cause birth defects and developmental delays. Zika virus can also be passed through sex and blood transfusions. These mosquitoes mostly bite during the day and night.
Earlier to 2014, exceptionally few travel-associated cases of Zika virus disease were recognized within the United States. In 2015 and 2016, huge episodes of Zika virus happened within the Americas, coming about in an increment in travel-associated cases in US states, broad transmission in Puerto Rico and the US Virgin Islands, and restricted nearby transmission in Florida and Texas. In 2017, the number of detailed Zika infection malady cases within the Joined together States begun to decline. In 2018 and 2019, there is no report of Zika virus transmission by mosquitoes within the continental US.
History on Zika Virus
Zika, a flavivirus transmitted basically by mosquitos within the class Aedes, was found in 1947 in Uganda. From the 1960s to 1980s, human contaminations were found over Africa and Asia, regularly accompanied by mellow ailment. The primary expansive flare-up of infection caused by Zika disease was detailed from the island of Yap (Combined States of Micronesia) in 2007, as the virus moved from south-east Asia over the Pacific. Amid a flare-up in French Polynesia in 2013–2014, Guillain-Barre disorder was connected to Zika contamination and cases of microcephaly in infant children were moreover reflectively connected to this outbreak.
The World Health Organization (WHO) gotten the primary reports of locally-transmitted contamination from Brazil in May 2015. In July 2015, wellbeing service authorities from Brazil detailed an affiliation between Zika infection disease and Guillain-Barre disorder in grown-ups. In October 2015, WHO gotten reports from Brazil of microcephaly in babies whose moms had been uncovered to Zika amid pregnancy. At this time, there was no confirmation of a causal connect between Zika disease and these neurological complications. In February 2016, as contamination moved quickly through the range involved by Aedes mosquitos in the Americas, WHO announced that Zika disease related with microcephaly and other neurological issue comprised a Public Health Emergency of International Concern. By the beginning of February 2016, neighborhood transmission of Zika disease had been accounted for from in excess of 20 nations and regions in the Americas and a flare-up numbering a large number of cases was in progress in Cabo Verde in western Africa. Past the scope of its mosquito vectors, Zika infection contaminations are relied upon to be conveyed worldwide by individuals as they travel and be transmitted by voyagers to sexual accomplices who have not been to places where the infection is endemic.
Causes and Transmission
Zika infection is transmitted essentially through the bite of a contaminated female Aedes species mosquito (Ae. aegypti and Ae. albopictus). These are similar mosquitoes that spread dengue and chikungunya infections. Mosquitoes end up been infected when they feed on an individual who is already infected with the virus, the infection at that point duplicates and spreads inside the mosquito so that when the infected mosquito bite once more, the infection is spread to another individual. Zika infection is transmitted to individuals principally through the bite of a contaminated Aedes species mosquito. These mosquitoes commonly lay eggs in and close standing water in things like basins, bowls, creature dishes, vases, and jars. They are forceful daytime biters, want to bite individuals and live inside and outside close individuals. Mosquitoes become tainted when they feed on an individual officially contaminated with the infection. Tainted mosquitoes would then be able to spread the infection to other individuals through chomps. The mosquitoes, for the most part, procure the infection while benefiting from the blood of a contaminated individual. After infection brooding for eight to ten days, a contaminated mosquito is competent, during testing and blood encouraging, of transmitting the infection for a mind-blowing remainder. There is no real way to tell if a mosquito is conveying the zika infection. Infected female mosquitoes may likewise transmit the infection to their posterity by transovarial (through the eggs) transmission, however, the job of this in supporting the transmission of the infection to people has not yet been characterized. Contaminated people are the primary bearers and multipliers of the infection, and filling in as a wellspring of the infection for uninfected mosquitoes. The infection courses in the blood of tainted people for a few days, at roughly a similar time, that they have Zika fever (see likewise clinical side effects). Aedes mosquitoes may secure the infection when they feed on a person during this period.
Symptoms
As several as four out of five individuals infected with the Zika virus haven’t any signs or symptoms. Once symptoms do occur, they typically begin 2 to seven days when an individual is bitten by AN infected dipterous insect. Signs and symptoms of the Zika virus most typically include Mild fever, Rash, Joint or muscle pain. Other signs and symptoms could include: Headache, Red eyes (conjunctivitis)
Side effects can final for a few days to a week. Individuals more often than not don’t get debilitated sufficient to go to the clinic, and they exceptionally once in a while kick the bucket of Zika. Once an individual has been contaminated with Zika, they are likely to be secured from future contaminations.
Complication from Zika virus infection
World Health Organization (WHO) has pronounced the spread of the Zika infection as a general wellbeing crisis because of the inconveniences that emerge from this infection. The most conspicuous difficulties include: extreme lack of hydration, inborn deformities, particularly microcephaly, premature delivery and stillbirth in pregnant ladies, untimely birth, eye issues in babies with Zika-related microcephaly, for example, abandon in the retina or the optic nerve, which could prompt visual impairment sometime down the road ,hearing weakness , Intense Disseminated Encephalomyelitis ( ADEM), which is irritation in the cerebrum and spinal rope that harms the myelin or the defensive covering of nerve strands, bit by bit prompting visual misfortune, and shortcoming to the point of loss of motion.
Microcephaly is an unprecedented clutter in which a baby’s head is much littler than typical due to irregular brain improvement whereas within the womb or in the blink of an eye after birth. Babies with this condition will regularly encounter formative delays afterward in life and a few may have vision absconds counting visual impairment. The issues influencing babies with microcephaly can extend from mellow to extreme and can now and then be life-threatening. Microcephaly can be caused by several hereditary and natural variables, counting down disorder and fetal introduction to an assortment of poisons. In any case, the number of microcephaly cases amid the Zika infection flare-up in Brazil was almost twenty times higher than regularly would be anticipated. Such an innate deformity has not been seen with any other flavivirus or other arthropod-borne infection.
Another complication of Zika virus is Guillain-Barre disorder, an uncommon condition in which the body’s safe system assaults portion of the apprehensive system.
This disorder too can be caused by several other infections. Side effects incorporate strong shortcoming and shivering within the arms and legs. Within the most serious cases, an individual may be nearly totally paralyzed and the respiratory muscles influenced, and the quiet will require hospitalization. Most individuals recuperate, but a few may proceed to encounter a few degrees of shortcoming.
Testing and Diagnosis for Zika virus
In the event that the patient has symptom to Zika virus and has side effects of Zika infection disease or a history or indications whenever during her pregnancy, Lives in or much of the time goes to a region with danger of Zika however does not have side effects of Zika infection contamination, Traveled to or had intercourse without a condom with an accomplice who lived in or headed out to a region with danger of Zika yet does not have manifestations of Zika infection disease, was presented to Zika and had birth abandons conceivably connected with Zika distinguished on a pre-birth ultrasound. Several types of testing are recommended based on these factors.
For Testing Symptomatic Pregnant Women: Symptomatic pregnant ladies with conceivable Zika virus presentation ought to get concurrent testing of serum and pee by NAAT and Zika virus IgM testing of serum as before long as conceivable, up to 12 weeks after indication onset. In expansion, for ladies with a conceivable presentation to both Zika and dengue, testing of serum for dengue by NAAT and dengue infection IgM testing too ought to be performed. A positive Zika virus NAAT result, in conjunction with a positive IgM result, ought to be translated as an intense maternal Zika virus. A positive dengue infection NAAT result ought to be translated as an intense maternal dengue virus. If Zika infection NAAT is positive on a single example but IgM counteracting agent tests are negative, rehash NAAT on recently extricated RNA from the same specimen. A positive Zika virus NAAT on either a serum or pee example in conjunction with a positive Zika IgM ought to be translated as corroborative for intense Zika virus disease and rehash NAAT isn’t recommended (Testing & Diagnosis for Zika Virus (CDC)).
For testing Asymptomatic Pregnant Women: Asymptomatic pregnant ladies with current potential Zika virus exposure (i.e., residence in or frequent travel apart with the risk of Zika) ought to be offered RNA NAAT testing 3 times throughout the physiological state. though there’s no way to verify the temporal arrangement of testing of asymptomatic pregnant ladies with solely NAT testing, testing at the initiation of prenatal care with 2 further tests performed throughout the course of the physiological state, coinciding with prenatal visits ought to be thought-about. For this cluster, testing for Zika virus immune globulin antibodies isn’t any longer habitually suggested as a result of IgM antibodies will persist for months once infection; thus, immune globulin results cannot faithfully verify whether or not AN infection occurred throughout the present physiological state versus before conception (Testing & Diagnosis for Zika Virus (CDC)).
Treatment and Vaccine
There is presently no cure for Zika virus disease and no vaccine to treat it. Scientists have begun the method of developing an immunization, however it’s expected to require years to develop one that might be wide accessible. As for now, the individual with the symptoms can treat it by getting a lot of rest, drink liquids to forestall drying out, take prescription, for example, acetaminophen to diminish fever and agony, and try not to take ibuprofen and other non-steroidal mitigating drugs (NSAIDS) until dengue can be precluded to decrease the danger of dying. On the off chance that you are taking drug for another ailment, converse with your human services supplier before taking extra prescription.
Prevention against Zika virus
Safety against mosquito bites at some stage in the day and early night is a key degree to save you Zika virus contamination. Extraordinary consideration ought to be given to the avoidance of mosquito bites among pregnant ladies, ladies of regenerative age, and youthful children. Personal assurance measures incorporate wearing clothing (ideally light-colored) that covers as much of the body as conceivable; utilizing physical boundaries such as window screens and closed entryways and windows; and applying creepy crawly repellent to skin or clothing that contains DEET, IR3535 or icaridin agreeing to the item name instructions. Young children and pregnant ladies ought to rest beneath mosquito nets if resting amid the day or early evening. Voyagers and those living in influenced zones ought to take the same fundamental safeguards depicted over to ensure themselves from mosquito bites. Aedes mosquitoes breed in little collections of water around homes, schools, and work locales. It is imperative to kill these mosquito breeding locales. In the course of sexual contact, use a condom to lessen the chance of having or spreading the Zika virus in case you or your accomplice lives in or has traveled to a place where there is a plague of Zika virus. Or keep away from sexual touch.
Conclusion
Zika virus emerged within the Americas, all of sudden, and spread quickly. Widespread infection by Zika virus was worrisome as a result of the virus had not antecedently existed within the Americas, and so nearly nobody was resistant to the virus; there existed the potential for many individuals to become infected. Like different mosquito-borne diseases, however, the eruption within the U.S and Europe were less in-depth than in the developing countries afflicted by Zika virus, a minimum of partially because of higher surveillance, mosquito management, and health care infrastructure. Zika virus infection in people seems to own changed in character whereas increasing in geographical vary. The modification is from an epidemic virus causing gentle sickness across equatorial Africa and Asia. From 2007 forward, Zika infection caused expansive flare-ups in already unexposed populations, and from 2013 forward, outbreaks joined with neurologic disorders as well as Guillain-Barre syndrome and nonheritable malformations, for reasons that aren’t however best-known. The long-run transmission of Zika infection is probably going to coincide with the world distribution of Aedes vectors. Person-to-person transmission, each vertically, from mother to fetus, and horizontally through sexual transmission, is additionally expected to continue, and that we anticipate that infections are carried wide by international travel. We can’t always prevent mosquitoes bite, we can at least try to be cautious about our surroundings. Before traveling to a foreign country, visit your doctors to get vaccinated requirements for the country one is traveling to. Although there aren’t any treatment and vaccine for Zika virus, scientists are currently working a cure for it and we hoped for it to be available soon.
Work Cited
Morain, Stephanie R., et al. “Stakeholder Insights from Zika Virus Infections in Houston, Texas, USA, 2016–2017.” Emerging Infectious Diseases, vol. 24, no. 11, 2018, pp. 2049–2055., doi:10.3201/eid2411.172108.
“Testing & Diagnosis for Zika Virus | CDC.” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, www.cdc.gov/pregnancy/zika/testing-follow-up/testing-and-diagnosis.html.
“About Zika Virus Disease | Zika Virus | CDC.” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, www.cdc.gov/zika/about/index.html.
Plourde, Anna R, and Evan M Bloch. “A Literature Review of Zika Virus.” Emerging Infectious Diseases, Centers for Disease Control and Prevention, July 2016, www.ncbi.nlm.nih.gov/pmc/articles/PMC4918175/.
“The History of Zika Virus.” World Health Organization, World Health Organization, 25 Jan. 2019, www.who.int/emergencies/zika-virus/timeline/en/.
Michael S. Diamond, Et All ”Zika Virus Vaccine Development: Progress In The Face Of New Challenges.” Annual Reviews of Medicine Med 2019. 70:32.1-32.15. 24 October 2018. Tamuk. Databases. 27 November 2018
“Zika Virus.” Baylor College of Medicine, www.bcm.edu/departments/molecular-virology-and-microbiology/emerging-infections-and-biodefense/zika. Administrator. Transmission of Zika Virus by Aedes Mosquitoes, www.zikavirusnet.com/transmission.html.
“Zika Virus.” Mayo Clinic, Mayo Foundation for Medical Education and Research, 21 Dec. 2018, Scott C. Weaver, Et All “Zika, Chikungunya, and other Emerging Vector-Borne Viral
Diseases.” Annual Review of Medicine. 2018. 69: 395-408. 28 August 2017. Tamuk. Databases. 28 November 2018. www.mayoclinic.org/diseases-conditions/zika-virus/symptoms-causes/syc-20353639.
“Zika Virus Disease: Symptoms, Complications, and Treatment.” Practo, Practo Health Wiki, www.practo.com/health-wiki/zika-virus-disease-symptoms-complications-and-treatment/21/article.
Wei, Tan Dawn. “Special Report: Zeroing in on the Zika Virus.” The Straits Times, 1 Feb. 2016, www.straitstimes.com/world/americas/zeroing-in-on-the-zika-virus.
Zika virus (ZIKV) is a vector born disease that was discovered in Ugandan monkeys in the 1940s. It was not until the 1950s that it was found that ZIKV was transmittable to humans. Mosquitos transmit it when they bite humans. This disease is more common in tropical warm climates where mosquitos are plentiful. Unlike most mosquito-borne diseases, ZIKV can be spread through sexual transmission giving this virus a larger swath of transmission possibilities (Hinkle, Brunner, Cheever, & Suddarth, 2014, p. 2150). People who contract ZIKV can present as asymptomatic or have a range of symptoms for 2-7 days. They may present with the following symptoms: a mild fever, rash, headache, conjunctivitis, or joint and muscle pain. The truly devastating nature of this disease is the effects it has on the developing fetus if the mother contracts ZIKV while pregnant, or up to a month before pregnancy (Khabbaz, 2019). If the fetus contracts ZIKV it is called Congenital Zika syndrome. This presents with the fetus most at risk for developing severe microcephaly, which is a very small head. In extreme cases, the fetal head may be partially collapsed. ZIKV can also cause Guillain–Barré syndrome in the mother/patient, which presents with muscle weakness that can rapidly develop into the patient becoming completely paralyzed (Medina-Cucurella, et al., 2019). The purpose of this paper is to discuss how evidence-based research on the ZIKV and pregnancy has been used to provide information for health care professionals to better identify, treat, or prevent this virus in pregnant patients. Through assessments, diagnostic tests, community resources, and educating patients we can increase the ability to prevent ZIKV from occurring during pregnancy (Hinkle, Brunner, Cheever, & Suddarth, 2014, p. 2150).
Assessment Data
There are several assessments the nurse should make when encountering pregnant patients. In regards to ZIKV, all pregnant patients should be asked about recent travel, being especially aware of places where documented outbreaks of the ZIKV have been reported. Ask the patient if they have traveled to a known place where transmission has occurred, then ask the patient if they have presented with any symptoms while on the trip or up to two weeks after returning. If the patient is at risk, maternal serum testing is used to diagnose ZIKV. The serum testing is only performed in a few locations, so the health care provider should contact their state health department to arrange testing for the patient (Killion, 2016). If the virus is confirmed in a pregnant mother, then close fetal monitoring via ultrasound should be done to look for microcephaly, intracranial calcifications or other anatomical anomalies (Killion, 2016). Ultrasounds are recommended to be done every 3-4 weeks, which is more than would be done in a low-risk pregnancy. If there is a reason to believe fetal infection has occurred, an amniocentesis (testing of the amniotic fluid) for ZIKV should be done. This is to confirm if the fetus has Congenital Zika Syndrome (Khabbaz, 2019). Amniocentesis may also be done to test for other complications, even if the fetus does not have evidence of fetal distress. The fetus that has been confirmed to have Congenital Zika Syndrome is also at risk for other congenital defects that may not be detectable by ultrasound alone. Some issues include decreased brain tissue, damage to the posterior eye, joints with limited ROM (range of motion), and increased muscle tone which may restrict the baby’s body movement post-birth (Khabbaz, 2019). If a baby is born with congenital Zika infection, they should receive eye screenings and tests to check for eye and other health problems, even if the baby appears to be in good health after being born. A multidisciplinary team is essential for the pregnant patient with ZIKV. The patient will need to be referred to a disease specialist, maternal-fetal medicine, and potentially other specialties (Killion, 2016). Education on prevention is the best course of treatment but it is not always possible. Cases of ZIKV must be reported to state and local health departments. These departments will report the case to the CDC (Centers for Disease Control) so that they can closely monitor cases of ZIKV. (Stockwell, 2018).
Age, Gender, and Genetic Makeup
Women of childbearing age who live in areas where ZIKV is prevalent are at the highest risk for contracting the virus before and after becoming pregnant. ZIKV is an arbovirus, meaning that it is carried by arthropods: an invertebrate that includes insects (vectors) (Khabbaz, 2019). “Zika virus is a single-stranded RNA virus of the Flaviviridae family, genus Flavivirus” (Khabbaz, 2019). It is transmitted to humans through the bite of the Aedes mosquito. These are the same mosquitos that spread Chikungunya and dengue fever (Todd, 2016). Testing for the disease is a challenge. The only way that the virus can be detected is by using reverse transcriptase-polymerase chain reaction (RT-PCR) testing (Todd, 2016). As stated previously this test is only available in a few places, which makes diagnosing a challenge.
Potential Cultural, Ethical, and Psychosocial Aspects
Nurses must be aware of how to handle the patient’s psychosocial health when dealing with ZIKV and pregnancy. Referring the patient to a counseling resource is recommended even before ZIKV testing is completed (Khabbaz, 2019). This is recommended due to the amount of information to process and understand regarding the disease and potential fetal outcomes associated with the virus. If the woman is living in an area where the virus is a continual threat, this would also cause the patient stress. Counseling and teaching are essential in the overall mental and physical health of the patient and baby. Since there is very limited access to mental health professionals and shortages in most affected countries due to poverty, this “can lead to more stigmatization, panic and anxiety stress, depression, to suicidal and other social issues in pregnant women and affected communities” (Tambo et al., 2017, p. 12). Most countries affected by ZIKV are below the poverty line (Medina-Cucurella, et al., 2019). This makes dealing with mental health issues especially challenging. “It is urgent to address the epidemiologic, clinical knowledge and skills gaps and ZIKV complications issues requires urgent sustained funding support on new and appropriate evidence-based long-term contextual programs and mitigation measures, survivor (s) and family educational and psychosocial counseling to psychiatry rehabilitation activities” (Tambo, et al, 2017, p. 12).
Evidence-Based Practice
The evidence-based practice article that was used is called: “Zika-Prevention Knowledge among Hispanic Women Living in Puerto Rico: A Cross-sectional Study.” The article’s objective was to determine the level of education in women regarding ZIKV exposure, its symptoms, potential complications, how the virus is spread, and precautionary measures for the Hispanic women living in Puerto Rico (Medina-Cucurella, et al., 2019). The results revealed that most of the women were aware of ZIKV and acceptable preventative measures. It also revealed a large number of the women were living in poverty, but most had health insurance (Medina-Cucurella, et al., 2019). A staggeringly low percentage of women received information regarding ZIKV through their primary care physician (PCP). Most heard information about ZIKV via the radio, news, or television. This study was mostly done with women in hospital waiting rooms. It is concerning that these women are not receiving adequate education, especially since they live within a city with a high incidence of ZIKV (Medina-Cucurella, et al., 2019). A huge part of nursing practice is patient education. While the women are receiving reproductive health care is a perfect opportunity to educate them on prevention and other pertinent information regarding ZIKV (Medina-Cucurella, et al, 2019).
Health Promotion and Recovery
Prevention is the only way to ensure ZIKV does not affect a developing fetus. Different forms of mosquito repellent should be discussed. Educating the patient on different forms of contraception is also imperative since ZIKV can be sexually transmitted. If the patient has ZIKV then the importance of frequent and vigilant prenatal care and ultrasounds needs to be emphasized. This can be a difficult thing to process and counseling services are strongly encouraged (Khabbaz, 2019). Regular pregnancy education should not be left out, even when dealing with something as traumatic as ZIKV. Patients should be taught about the signs and symptoms of preterm labor, rupture of membranes, and when to seek medical help or call their PCP.
Community Resources
As a nurse, it is important to help identify community resources for the patients, because these patients may not know that these resources exist or how to find them. There is a wealth of information on the CDC’s website (https://www.cdc.gov/pregnancy/zika/protect-yourself.html), and their phone number is 1-866-626-6847. The following website provides e-mail and chat support in both Spanish and English for patients with ZIKV or general pregnancy questions: https://mothertobaby.org/contact-expert/. (‘Welcome to MotherToBaby’, 2018).
Conclusion
ZIKV is a mosquito-spread condition that can present with distressing fetal anomalies. The hallmark finding in fetal development is microcephaly. Prevention is the best measure of protection, whether that means contraceptives or bug repellent. Education is vital, and nurses play an important role in assuring that patients receive adequate education on ZIKV. The stress of having a baby with potential complications can be psychologically challenging. Services and referrals should be recommended to the mother to help maintain her mental health.
Hinkle, J. L., Brunner, L. S., Cheever, K. H., & Suddarth, D. S. (2014). Brunner & Suddarth’s textbook of medical-surgical nursing. Lippincott Williams & Wilkins.
Khabbaz. (2019, January 28). Clinical Evaluation & Disease | Zika Virus | CDC. Retrieved October 3, 2019, from https://www.cdc.gov/zika/hc-providers/preparing-for-zika/clinicalevaluationdisease.html.
Khabbaz, R. (2019, June 13). Patient Counseling for Pregnant Women on Zika and Pregnancy | CDC. Retrieved October 3, 2019, from https://www.cdc.gov/pregnancy/zika/testing-follow-up/patient-counseling-pregnant-women.html.
Khabbaz, R. (2019, May 14). Birth Defects | Zika virus | CDC. Retrieved October 3, 2019, from https://www.cdc.gov/zika/healtheffects/birth_defects.html.
Killion, M. M. (2016). Zika virus update. MCN, The American Journal of Maternal/Child Nursing, 41(4), 252. doi: 10.1097/nmc.0000000000000246
Medina-Cucurella, E., Acevedo-Canabal, J., León, J. D., Martínez-Torres, R., Cruzado-Ramos, G., & Romaguera, J. (2019, October 3). Zika-prevention knowledge among Hispanic women living in Puerto Rico: A cross-sectional study. Retrieved October 3, 2019, from https://www.pubfacts.com/detail/30576578/Zika-prevention-Knowledge-among-Hispanic-Women-Living-in-Puerto-Rico-A-Cross-sectional-Study.
Stockwell, S. (2018). The CDC updated guidelines for congenital Zika. AJN, American Journal of Nursing, 118(2), 14. doi: 10.1097/01.naj.0000530232.22909.7c
Tambo, E., Madjou, G., Khayeka-Wandabwa, C., Olalubi, O. A., Chengho, C. F., & Khater, E. I. (2017). Ethical, legal and societal considerations on Zika virus epidemics complications in scaling-up prevention and control strategies. Philosophy, Ethics, and Humanities in Medicine, 12(1). doi: 10.1186/s13010-017-0046-8
Todd, B. (2016, April). Zika virus: An unfolding epidemic. Retrieved October 2, 2019, from https://www.nursingcenter.com/journalarticle?Article_ID=3410173&Journal_ID=54030&Issue_ID=3409942.
Welcome to MotherToBaby. (2018, December 21). Retrieved October 3, 2019, from https://mothertobaby.org/.
ZikaVirus. (n.d.). Retrieved October 2, 2019, from https://www.nursingcenter.com/resources/clinical-topics/zika-virus.
Emerging Infectious Diseases (EID) are referred to as diseases that are newly recognized or diseases whose incidence has increased over time. It may be a disease that we know of and that still persists. When some of these diseases do not directly affect us, these diseases are not given attention and are ignored. The significance of the Environment, Vector, and the Host play a pivotal role in predicting and managing diseases. A disease might be a focus of renewed concern because their may be a genetic change, which can make the disease more serious, become resistant to antibiotics, or the disease might move into new communities. People who would be carrying the disease would easily spread it to more vulnerable people, and that would require a high level of herd immunity to prevent it from spreading.
A few drivers of emerging infectious diseases have contributed to the re-emergence andspread of the Zika Virus. Over time, an epidemic of Zika has spread throughout North and South, “estimating 3.9 billion people at risk” (Shragai, T., Tesla, B., Murdock, C., & Harrington, L. C., 2017). The growing burden of the Zika virus has raised questions about how the disease itself, its transmission routes, and people’s behaviours have evolved as it spread into new areas and places that were never thought of being encountered. This mosquito-borne virus infection has spread because of the living intermediate, known as the vector. To define its environment, the biotic and abiotic factors of the disease agent have a major influence on the host, which involve humans and animals in a particular type of climate in a defined environment.
Climate change has contributed to the re-emergence of Zika virus. Environmental drivers such as “temperature, humidity, and rainfall patterns” have induced the transmission itself (Shragai et al., 2017). When the mosquito interacts with the abiotic environment, factors such as “climate, water storage, and urbanization and land use” come into play when the mosquito comes into contact with them (Shragai et al., 2017). Interactions with the biotic environment, including “competitors, the number of hosts available, and human movement and change” are the living intermediates’ sources for progression (Shragai et al., 2017). How “competent the vector is, its resistance to insecticides, its life history and its host preferences” are factors that make up the geographic variation in the mode of transmission (Shragai et al., 2017). The disease agents’ “capacity to transmit disease, its abundance, and its distribution” then contribute to the overall level of global disease transmission of the Zika virus (Shragai et al., 2017).
The type of environment is also an important part because it poses as the vectors’ breeding grounds, particularly still water. It creates space for the vector population to flourish in the natural ecosystem. Along with the environment, poverty is associated with higher risk of infectious disease. It may lead to “inadequate vector control and prevention programs and negligible healthcare infrastructure” (Mavian et. al, 2019). Warming temperatures and more rainfall contribute to the re-emergence of the Zika virus because the vector can easily adapt to its surroundings and produce in high amounts in warmers temperatures. This is a result of climate change and global warming. Human demographics and behaviour is another driver that contributes to the re-emergence of the Zika virus. The movement of humans throughout history has introduced certain species into certain populations. Activities such as “deforestation due to human settlement and agriculture, involving irrigation” affect the transmission and increased production of mosquitos (Mavian et. al, 2019).
It also all depends on the size of the population, meaning the larger and denser the population is, the faster the Zika virus can spread. Tropical islands in the Pacific and Indian Ocean inhibit a tropical climate, with hot and humid weather, abundant rainfall, and a wet and dry season, therefore mosquitos are more likely able to develop and adapt to their surroundings in this particular climate and weather. As the Zika virus’ “incubation period is 3-12 days”, it is an “epidemic in the Caribbean, Central and South America” (Poulakou & Plachouras, 2016). Characteristics of the Zika virus, particularly people at risk, include travelers and residents. There had been a reported “sexual transmission of the Zika virus around June 14, 2016 in central america” (Poulakou & Plachouras, 2016).
Bibliography
Mavian, C., Dulcey, M., Munoz, O., Salemi, M., Vittor, A. Y., & Capua, I. (2019). Islands as Hotspots for Emerging Mosquito-Borne Viruses: A One-Health Perspective. Viruses (1999-4915), 11(1), 11. Retrieved from https://doi-org.ezproxy.langara.bc.ca/10.3390/v11010011
Poulakou, G., & Plachouras, D. (2016). Planet’s population on the move, infections on the rise. Intensive Care Medicine, 42(12), 2055. Retrieved from https://eds-b-ebscohost-com.ezproxy.langara.bc.ca/eds/pdfviewer/pdfviewer?vid=0&sid=cfe49a49-1a48-4610-b9c3-87b53721656f%40sessionmgr120
Shragai, T., Tesla, B., Murdock, C., & Harrington, L. C. (2017). Zika and chikungunya: mosquito-borne viruses in a changing world. Annals Of The New York Academy Of Sciences, 1399(1), 61–77. Retrieved from https://doi-org.ezproxy.langara.bc.ca/10.1111/nyas.13306 https://doi-org.ezproxy.langara.bc.ca/10.3390/v11010011
Cancer has been among the leading causes of death throughout the world for decades, devastating many families with its commonly low survival rates and limited treatment options. In particular, Glioblastoma, arguably the most aggressive form of cancer, is fatal with the median survival rate being 10 to 12 months[1] (even when accompanied with treatment) due to how developed the grade IV tumour is. Because of this reason, it is also one of the most researched topics within oncology with promising treatment techniques being discovered every year. One of these potential treatments involves the use of an adapted form of the Zika virus, a pathogen which was responsible for disease epidemics primarily from 2015 to 2016, particularly in Brazil. Scientists have found a way to alter the virus and use it as a means to benefit the treatment of certain malignant tumours. One of the prime effects of the virus is that it hinders neural development in fetuses, causing the microcephaly seen in children. This characteristic of the virus presented itself as an ideal mechanism to study within cancer research, as the reducing effect of the virus could be directed into slowing cell division instead of neural development, giving it good potential for future testing.
The cycle of the Zika virus
The Zika virus (ZIKV) is categorised as a flavivirus and was first identified in the Zika forest in Uganda (1947)[2] when it was noticed in a rhesus sentinel monkey and was consequently isolated. The first record of a ZIKV infection in humans was in 1954, Nigeria[4], where a young 10 year old child was found to be carrying the virus in the midst of an epidemic of jaundice taking place in Africa.
The Zika virus is found within the family of Flaviviridae and the genus Flavivirus and is classified as an Arbovirus. It is a single stranded RNA virus in an icosahedral structure, with similarities to other members of the Flavivirus genus such as the West Nile virus. An Arbovirus is an arthropod borne virus which is carried throughout nature by the means of biological transmission from susceptible vertebrate hosts to hematophagous (vector) arthropods including mosquitoes.
The virus’s main means of transmission is through the bite of an Aedes Aegypti mosquito, found across the world but its place of origin as well as its highest population, is in Africa. The females of the Aegypti species must bite animals or humans as they require certain proteins to activate the vitellogenin gene, starting the production of yolk protein which then causes egg production within the ovaries. They get these proteins as well as others which help to sustain the eggs, from the components of blood. So the cycle of ZIKV transmission begins when the mosquito first feeds on the blood of a person who is a carrier of the Zika virus. The ZIKV in their blood is then transferred to the mosquito, where it is ingested and then the virus proceeds to reproduce in the epithelial tissue of the midgut. As the ZIKV replicates, it spreads to glands, most importantly the salivary glands where it remains for an incubation duration of 10 days. After this time, the mosquito now becomes a vector to the ZIKV, gaining the ability to transfer it to another being through the exchange of fluids when feeding on blood. As the feeding takes place, the virus infects the other organism’s dermis layer and replication occurs. It can also go on to infect the fetus of those pregnant by passing through the placental barrier. This sylvatic cycle then continues.
Why ZIKV was an ideal virus to study within oncology
The virus infects many people, however most cases are merely mild infections and are not harmful, whereas the infection is more concerning for pregnant women. This concern originates from the evidence that ZIKV causes different defects in the fetus. For example, congenital microcephaly, cerebral atrophy, intracranial calcifications (calcium deposits) and hydranencephaly (missing front hemispheres). These symptoms stem from a reduced effect of neural development, caused by the mechanism of the ZIKV. These reducing and hindering characteristics of the virus, presented themselves as ideal aspects to study within the field of oncology, with the intention that with further research and investigation of ZIKV, the reducing effect could be channeled into limiting the uncontrollable cell division and mutation that defines cancer.
Overview of GBM treatment options
A particularly aggressive form of cancer is Glioblastoma Multiforme (GBM). Glioblastoma is defined by the National Cancer Institute as ‘a fast-growing type of central nervous system tumor that forms from glial (supportive) tissue of the brain and spinal cord’[3]. Although it can be found in the spinal cord, it is much more common in the brain which is why Glioma is used as a general term to identify primary brain tumors. Gliomas can be graded ranging from grade I to IV, with IV being highly malignant as well as invasive, compared to grade I where the cancer can often be eliminated with surgery. So far, no exact carcinogenic causes of the tumors have been identified and the only risk factor is exposure to high levels of ionising radiation, which may cause a genetic mutation, unlike other cancers where there are multiple risk factors such as smoking or obesity. The most common site of tumor formation is the supratentorial region of the cerebral hemisphere. Glioblastoma is particularly fatal due to the detrimental effect of the uncontrollable mitotic activity in the brain hemispheres. This formation of a mass can impair certain functions, depending on its location. For example, if the mass disrupts the frontal lobe tissue, psychiatric disturbances could occur, or if in the temporal lobe, hearing or vision could be affected. Seizures are also common as well as hemorrhages, which are likely to progress to a fatal level.
Evaluation of common treatment options
As of today there are no definitive curative treatment methods but there are treatments to prolong life for up to 3 years more, usually aimed at shrinking the tumor. Surgery to resect the tumor is often the most invasive but effective method of treatment. The surgery begins with the neurosurgeon performing a craniotomy to allow access through the skull and into the portion of brain tissue where the glioma is situated. There are multiple types of craniotomies such as stereotactic craniotomies where imaging such as MRI or CT scanners are used to allow the surgeon to distinguish between healthy brain tissue and cancerous tissue. Another method used for visualisation is fluorescence guided surgery where fluorescein is used to make the tumor glow. The surgeon will then resect as much of the tumor as possible since recurrence of the tumor is expected at anything over a 2cm margin of the resection, whilst being careful not to damage too much healthy tissue as this could have disastrous effects. These effects could be loss of speech, memory, sight, movement etc, all depending on where the primary site of the tumor is located. In order to avoid any complications like this, the surgery can be done whilst the patient is fully conscious. This is called intraoperative brain mapping. Awake surgery is common when the glioma is less defined and has unclear margins. The neurosurgeon needs constant feedback to see if any key brain functions have been affected, due to the destroyal of the brain tissue.
After an attempt at surgery or if the tumor was inoperable, the next stage of treatment is generally chemotherapy and radiation therapy. The chemotherapy most commonly used is temozolomide with it being used everyday during radiotherapy, then six maintenance cycles after. Temozolomide has a cytotoxic effect through methylation, which suppresses gene transcription and stops the activity of the DNA. Targeted drug therapy can also be used which eradicates specific cells, leaving surrounding brain tissue undamaged by the toxic effects often inflicted during other therapies such as radiation or chemotherapy.
Why Glioblastoma is difficult to treat
Despite all of these options, Glioblastoma is still extremely difficult to treat as a result of its place within our most vital cells and its predilection to recur. Due to its location in the brain and spinal cord, most treatment damages large sections of vital healthy tissue as well as cancerous cells. Depending on the number of damaged cells, the patients could lose partial function of certain regions of their brain, or nerves in the spinal cord could be affected. This can be avoided by attempting to restrict the range of radiation or chemo but that increases the risk of recurrence since not all of the tumor will have been destroyed which allows the cancer to continue to divide. However there are always multiple clinical trials or preclinical trials as well as in depth research taking place, with the purpose of finding many more effective treatment options of Glioblastoma.
Virotherapy evaluation
One of these preclinical trials is investigating the adaptation of the Zika virus and its treatment of Glioblastoma. This is Virotherapy, a type of targeted therapy and is the method of changing gene expression in viruses to convert them into therapeutic agents capable of oncolytic activity.
Virotherapy comes with many beneficial aspects. Arguably the most important advantage is that replication of the virus only takes place within malignant cells. This therefore prevents compromising any healthy tissue for the sake of stopping cell division. The selected viruses only lyse tumor cells due to the particular cell surface receptors on their membranes, meaning the DNA of healthy cells remain unchanged unlike in chemo and radiotherapy where the field of treatment is more generalised. Another advantage of virotherapy is its ability to mark tumor cells which have dissipated around the body via the bloodstream, instead of being limited to a single large collection of malignant cells in one location. So the cancer can be potentially eradicated all at once, instead of in degrees, drastically cutting down on treatment time.
On the other hand, virotherapy does have some disadvantages, the main one being the chance of the immune system clearing the virus before any oncolytic activity has the chance to take effect. This is due to the body recognising the virus as foreign and prompting an immune response. This means that the virus does not always get the chance to lyse the tumor cells and eliminate the cancer so the treatment doesn’t guarantee success, potentially wasting time which could have been spent doing more tried and tested treatments. However, many doctors understand this and don’t use virotherapy as a stand alone method but rather incorporate it into other treatments such as chemotherapy and radiation. The multiple treatments can then work together to maximum effect ensuring the patient is getting the most effective treatment plan.
Preparation of the treatment
The Zika strain used was the Dakar 41519 and the Cambodian FSS13025 strain, developed from its complementary DNA chain. The Cambodian strain was chosen for mutagenesis as the clone was easier to access. The Dakar strain was passaged through a RAG-1-deficient (immunodeficient) mouse 4 times, to create a variant of ZIKV more inclined for infection due to a mutation in its NS4B gene. The Cambodian ZIKV was added to a diluted Temozolomide solution with the dissolution of phosphate buffered saline and ZIKV was added at a multiplicity of infection of 5.
Effectiveness of the ZIKV
The ZIKV was then inserted into the glioblastoma stem cells and an increase in apoptosis occurred. Apoptosis showed that the virus was successful in infecting the cells as there was more programmed cell death resulting in the shrinkage of the tissues, something that unaffected cancer cells are unable to do as the apoptotic pathway is dysfunctional. The B cell lymphoma-2 (Bcl2) expression was also regulated. This is a gene that can be responsible for either limiting apoptosis or inducing it, so is extremely important in the cell cycle. Overall, the virus was successful in treating the glioblastoma stem cells and inducing the microRNA 34c (MiR34c) expression which is a family of RNA that suppresses tumor growth.
Evaluation of the first stages of the ZIKV and GSCs trial
Overall, the study seems to have a solid foundation for continuation of a clinical trial as this is just its first stage out of many phases left to come. This study is not yet at a clinical trial level yet, instead it is in a period of preclinical testing. This means the treatment is not developed enough yet to test on humans, and remains in the lab. Generally, the preclinical studies are a result of extensive research channeled into a particular treatment whether it be vaccinations or antivirals and so on, or in this case, a virotherapy drug. The first stage of a preclinical trial is testing on artificially cultured tissue which was made to replicate whichever type of cell the treatment is focused on, in this case glioblastoma cells. The cells used in this trial were stem cells developed into GSCs. Possibly the most important aim of this stage is to test the drug’s efficacy. It allows scientists to observe the subcellular effects of the treatment and allows them to evaluate if it is effective against the targeted cells. If it is not then the drug is either altered further to improve the efficacy or sometimes discarded altogether if the treatment is deemed unsuccessful. Testing on animals usually follows this. This is done to observe any side effects the animals may have that could transfer to humans when they receive the treatment. Animal testing is always a heavily debated topic and presents both advantages and disadvantages although it is still widely used within testing for cancer treatments as it can benefit millions of patients.
This preclinical trial of the ZIKV and GSCs appears to have gone well. The efficacy of the virotherapy was confirmed in the studies and shown by the apoptosis of the cells, and there weren’t any complications to do with damage of the healthy stem cells. Most substances don’t advance past this stage of lab testing due to a lack in efficacy so this treatment does show promise compared with some other attempts at cancer treatment.
However, although the trial has not faced any major setbacks yet, the preclinical testing is not fully developed yet since no animal testing has taken place. This means that there could in fact be issues with the virotherapy when introduced to full working organisms but we are currently unaware of them since the treatment has not been tested that far yet. Therefore this lack of development in the preclinical trial is its main downfall as future problems may remain uncovered.
ZIKV as an enveloped, positive-sense, single-stranded RNA virus, belonging to the family of flavivirde.(1-3) The rapid geographical expansion and the rampant effect of zika virus (ZIKV) in the recent years have posed serious threat to human life, which lead World Health Organization to declare a Public Health Emergency of International Concern (PHEIC) against this flavivirus in 2016.(4) Binding and fusion of a virus with the host membrane is the first and one of the most crucial steps in the life cycle of all enveloped viruses. Therefore, it is essential to understand the structure and pathogenicity in order to develop therapies for prevention.(5) The cryo-EM structure of ZIKV helped elucidated the structural proteins of ZKIV. The structural protein is mainly composed of pre-membrane (prM/M), envelope (E) and capsid (C) protein. All these proteins are important components of fusion and binding events into host cells. Current research indicates a fusion event takes place in the acidic endosomal environment which triggers an irreversible conformational change of ZIKV’s three-domain envelope glycoprotein (E).(6) With the help of structural infection of ZIKV, researchers are trying to develop neutralizing antibodies against ZKIV to abate the infection and reduce the risks from ZIKV. The envelope protein is of particular interest because it helps mediating viral assembly, entry, and fusion hence being the main antigenic target for neutralizing antibodies. Therefore, development of neutralizing antibodies for the E protein could be the best therapeutic approach to offer protection against infection.(7)
Introduction
Zika virus (ZIKV) is a mosquito borne virus first isolated in 1947 from a sentinel rhesus monkey in Uganda.(8) This single stranded RNA virus has been associated to many other viruses like dengue virus, Chikungunya virus and West Nile virus, as they belong to the same the genus of Flavivirus.(9) The main transmission source of ZIKV is Aedes aegypti mosquito but some additional means of transmission are sexual, congenital or in some cases by blood transfusion. In usual cases 80% patients are asymptomatic for 3-12 post exposing to infection. The most commonly reported symptoms are fever, rash, headache and fatigue. (10-11) ZIKV is also linked to some severe symptoms where neonates were reported with microcephaly and increase in congenital CNS malformations. Furthermore, reports have suggested adults suffering from Gullain-Barre syndrome and meningitis. This indicates a strong link between ZIKV infection and CNS abnormalities. Recently, there has been upsurge in ZIKV infection and became the matter of concern do to the harm ZIKV can pose to human life.(12-13)
Although its first major outbreak was in 2007 on Yap island and Micronesia, the recent emergence of ZIKV in 2017 raised global concerns, by affecting millions in 84 different countries including the United States.(14) Furthermore, the World health organization (WHO) declared a public health emergency of international concern in 2016, when ZIKV infection was associated with microcephaly and Guillain barre syndrome.(15) Knowing the potential threat of ZIKV to the mankind, researchers are study the structure of the Zika envelope protein and develop better vaccines for treating Zika virus.
Like all the flaviviruses, the ZIKV genome is translated into extended polyprotein in the cytoplasm of the host cells. Further this polyprotein is cleaved by viral/host proteases into structural and non-structural proteins. The structural proteins comprise of three major components namely: capsid (C), membrane precursor/membrane (prM/M) and envelope (E) protein which help in forming the virus particles. Further, there are total seven non-structural proteins (NS1, NS2a, NS2b, NS3, NS4a, NS4b, and NS5) responsible for genome replication, handling polyprotein and antagonizing host response.(16-17)
Along with this, there is an untranslated region bordering in 5’ and 3’ flanking at the end. Additionally, similar to other enveloped viruses, in the life cycle of ZIKV, binding and fusion is one of the key events allowing the entry of virus into the host cell. It is traced that the E protein plays a major role in the event of binding and fusion of the virus. In order to develop vaccines against this virus, it is very crucial to understand the pathogenesis of the virus better.(18) Scientists are trying to elucidate the structure of this virus, and for the first time Richard Kuhn et. al. reported the Cryo-EM structure of mature ZIKV, which offered a lot of information to comprehend the unique features of this virus. It was elucidated, this virus has icosahedral arrangement with of 180 copies of E and M protein each, where E dimers surrounds the capsid. The prM/M has a M-loop and stem & transmembrane region (M-TM) which helps anchor the protein to the host lipid membrane. Furthermore, the E protein is mainly accountable for receptor viral assemble, binding and fusion. It mainly comprises of four domains which are: i) stem (E-stem) and transmembrane (E-TM) domain, ii) Domain I (DI), iii) Domain II (DII) and iv) Domain III (DIII) accountable for different functions. The stem transmembrane domain is responsible for membrane support. In the E protein, -barrel domain (DI) acts as a bridge between DII and DIII.
Further, the fusion loop (FL) is at the edge of DII has hydrophobic sequence, and is known to interacts with the with the host lipid bilayer during the fusion event. Like all other flaviviruses, DIII comprises of the receptor-binding site also carrying an important role during the fusion. (18-19)
The zika virus has three main phases in its life cycle, i) immature (non-infectious), mature (infectious), and fusogenic (binding phase). The virus is in the non-infectious state when it enters host cell via endocytosis. Due to the acidic environment in the endosomes, the E protein goes under an irreversible conformational change and the dimer is transformed into a trimer leading to fusion event. In the ER, this newly formed virus offspring forms immature virions which comprise of 60 E: precursor-membrane (prM) heterodimers. This is followed by the maturation phase in the trans-Golgi, where the acidic pH stimulates the restructuring of the E-prM heterodimers into 90 E:M homodimers. The immature structure has its cleavage site of prM exposed, where furin can (a host protease) slices prM into pr and M protein, leading to maturation. In the immature virus pr protects the fusion loop but after slicing the pr, fusion loop is exposed allowing the virus for pH-mediated fusion.(19-21)
Understanding the structural features of the virus is very important in the process of therapeutics development. Monoclonal antibodies (mAb) have been a hot subject for drug discoveries, and for years they have been used for variety of diseases like cancer, inflammatory diseases, neuro-degenerative diseases and infectious diseases. Development of mAb against flaviviruses is a very remarkable strategy to fight the infection. The mAb can safeguard against flavivirus infection at numerous steps which can impeding virus attachment to the host cell membrane, disrupt membrane fusion of virus, or it can be by triggering Fc-dependent effector functions. Although the posed advantages, weak/non-neutralizing antibodies at a sub-neutralizing concentrations may lead to antibody-dependent enhancement (ADE) of infection, an incident where the antibody helps facilitate the entry of virus via the Fc receptor (not expressed in all the cells) and increasing the infection rate.(22)
Therefore, for the flaviviruses, E-protein because of its functions remains a common target for generally known neutralizing antibodies. As discussed earlier, the three domains in E-protein are very important for the receptor identification, attachment and fusion events, hence mAb targeting E-protein can help stop infection by acting at the first step. However, there are antibodies against non-E proteins, mostly non-neutralizing, making them less favorable for the therapeutics approach. Hence, neutralizing antibodies with E protein as the antigenic targeting site are being looked upon as a promising solution in the development of better therapeutics interventions for ZIKV. In this study six monoclonal antibodies (mAbs) were developed for ZIKV by immunizing the mouse with live virus and enhancing with either infectious virus or recombinant E proteins. This report talks about the four of the mAbs (ZV-48, ZV-54, ZV-64, and ZV-67) neutralized infection of ZIKV to varying degrees, and also two ZV-2 and ZV-13 inhibited infection poorly against ZIKV.(23)
Results and Discussion
Testing neutralizing activity of ZIKV in vitro
The monoclonal antibodies developed were tested against ZIKV E (envelope), ZIKV E-FL (fusion loop mutant), ZIKV DIII, WNV E (West Nile virus envelope), and DENV-4 E (Dengue virus envelope) with the help of ELISA. The results indicated all the mAbs were specific to ZIKV DIII, except ZV-13 having cross reactivity against the WNV E. All the rest of mAb possessed minimal cross reactivity against WNV E and DENV4 E strain. To further perform primary analysis and test the efficiency of mAb, focus reduction neutralization tests (FRNT) were carried out. This is a widely used assay to test the neutralizing capability of the mAbs against specific virus. The test was carried out for various African and American ZIKV strains (H/PF/2013, Paraiba, Dakar, MR-766). Six mAb were incubated along with different strains and the result was measured as relative infection %. The results indicated ZV-13 and ZV-2 failed to neutralize against all the ZIKV strains in comparison to the other mAbs. Furthermore, the results also indicated, ZV-48 and ZV-64 also show reduced neutralization effects in some ZIKV strains. The reason for this is not clear.
Binding affinity of ZIKV mAbs
So far, the neutralizing efficiency of all the six monoclonal antibodies was tested, but the discrepancies within each mAbs were not addressed. One possible reason for this would be different binding site, so to understand this each mAbs were tested using biolayer interferometry. This is an analytical technique used for measuring molecular interactions. The biosensor tip is immobilized with protein and flowed with the sample. Any interactions would result in wavelength shift due to increase in optical density. This technique helps determine the binding affinities, binding, rate of dissociation and association.
To perform this assay, six mAbs were immobilized on different sensor chip and recombinant DIII was administered in the system. The antibody having maximum interaction with the DIII would indicate they are more neutralizing and further having greater binding affinities for the recombinant protein. Out of all the mAbs, KD equilibrium value for ZV-54 and ZV-67 was less than10 nM in contrast to ZV-64 and ZV-48 with the KD equilibrium ~ 35 nM, demonstrating highest binding affinity of ZV-54 and ZV-67 to the DIII. Furthermore, the half-lives of ZV-54 and ZV-67 was 33 and 13.8 min respectively, indicating the slowest dissociation rates when compared to ZV-64 and ZV-48 with half-lives of 1 and 3.2 min. This experiment further helped determine the discrepancies between all the mAbs and indicated the strength of ZV-54 and ZV-67.
Although some of the mAbs showed neutralization effect, it was still not clear whether they are responsible for antibody dependent enhancement or not. For neutralization, antibodies should be in sufficient stoichiometry, or the antibody help facilitate the virus in and increase the infection. Therefore, to test the degree of ADE and antibody concentration dependency an assay was performed on K562 cells expressing Fcγ receptor II for ZIKV and DENV-2. All the mAbs showed variable level of enhancement in infection, but the most neutralizing mAbs ZV-54 and ZV-67 showed ADE only at sub neutralizing concentrations. This means given an appropriate amount of these mAbs, the chances of ADE could be lowered.
mAbs binding on DIII
Although the binding affinity of all mAbs had been identified, it was unclear how the antibodies reacted on a structural level. To understand the structural basis of the interaction between the antibodies and DIII of ZIKV X-ray crystal structures were generated for all the DIII with four antibody complexes (ZV-2, ZV-48, ZV-64 and ZV-67). The results indicated, ZV-2 and ZV-67 were binding near heavy chain region, whereas ZV-48 and ZV-64 engaged at DIII by the light chain domains. From the results, the binding of ZV-48 and ZV-64 appeared to be very similar and therefore the further docking studies were carried out to determine the binding site of all the mAbs. Docking results indicated ZV-2 and ZV-67 bound to different epitopes and therefore, should not compete with each other during binding. On the contrary, ZV-67 and ZV-54 recognized same site on DIII leading to competitive binding. To experimentally prove this docking results, competitive binding assay were carried out. To perform the competitive binding, once ZV-67 was immobilized, and ZV-2 and ZV-64 when introduced could easily bind to the DIII, but ZV-54 could not bind portraying both the mAbs bind to the same determinants of the DIII. Similarly, when ZV-48 was immobilized, ZV-67 and ZV-2 captured on the DIII but due to competitive binding, ZV-64 was blocked. All the outcomes reinforced the docking analysis of three different epitope binding site.
In vitro studies
After establishing the ground in vitro and doing computational analysis, the results were indicative about the nature of the neutralizing effect of mAbs against the ZIKV infection. Therefore, to further validate the results, the effect of mAbs were tested in vivo on mice deficient in INF signaling. These mice were subjected to either non-binding control antibodies or anti ZIKV mAbs. In this experiment, two of the most neutralizing antibodies were chosen based on all the results obtained before. The results found indicated, increased level of ZIKV RNA in the serum of mice when treated with CHK-166 (control) in comparison to ZV-54 and ZV-67. Also, when the weight was measured for all the mice, control model showed reduced weight when compared to mice treated with ZV-67 and ZV-54. Furthermore, the survival analysis was also constant with the previous results, indicating reduced viremia and high survival rates in presence of the mAbs (ZV-67 and ZV-54). All the results were indicative of the neutralization capacity of the generated mAbs.
Conclusion
ZIKV has raised global concerns in the past, and due to the lack of vaccines available to treat this infection hence, it is very crucial to understand the structure of the ZIKV and try to develop vaccine for this harmful infection. To take a step further in the vaccine development for ZIKA virus, a group of mAbs were developed against ZIKV which could be a potential vaccine. The research focused on developing mAbs and acquire an understanding of epitopes identified by neutralizing antibodies. Mice were inoculated with ZIKV and the specific mAbs generated against ZIKV were analyzed. All the results suggested, four mAbs had binding affinity to ZIKV DIII, and further neutralized infection of ZIKV Asian strain. Out of those four, ZV-54 and ZV-67 proved to be more potent in neutralizing against other ZIKV strains whereas, ZV-48 and ZV-64 has a lower inhibitory action against African ZIKV and American strains. Furthermore, on analyzing the sequence of ZV-48 and ZV-64 the results indicated they are sibling clones’ due to the similarity in the VL region. In contrast, the findings also suggested ZV-54 and ZV-67 are related mAbs due to the similarity in VL and VH sequences. After the successful identification of the DIII binding epitopes of all the mAbs, in vivo studies carried out implied ZV-54 and ZV- 67 act as a defense means against an African ZIKV strain. Overall, this research introduced newly identified monoclonal antibodies for ZIKV DIII, with neutralizing effect, which could be used as in diagnostic assay or offer direction for development of preventive antibodies for pregnant women, or can also serve as a therapeutic antibody.
Birth defects are defined as one of the leading causes of infant deaths in the United States. It is not easy to detect the problems at early stages, and some children are put under threat as soon as they are born. Many babies are born with some parts of the body missing, malformed, or damaged. The defects of a head are the most frequent cases. Microcephaly is a defect that may influence brain development. It is a clinical condition that is usually characterized by having a smaller-than-normal head with less than -2 of standard deviation (Woods & Basto, 2014). The peculiar feature of this defect is its dependence on many genetic and environmental factors at the same time. Children with microcephaly suffer from numerous developmental issues.
Clinical Signs and Symptoms
Microcephaly is a developmental pathology that has one primary sign that cannot be neglected – the size of a child’s head is significantly smaller than that of other children’s heads of the same age and sex (Liuzzi et al., 2016). The child’s head should be measured and compared with the measurements given in specific charts. There are no special tests to determine this pathology before a baby is born. Sometimes, an ultrasound scan can be used to identify this problem in the third trimester. Additional microcephaly symptoms are hyperactivity, backward-sloping forehead, delays in speech and movement, difficulties incoordination, and facial distortions (Madhukark, Bhaysaheb, Babasaheb, Tukaram, & Balkrishna, 2016).
Epidemiology
Microcephaly is a rare condition in the United States. 2-12% per 10,000 of life birth includes the cases of microcephaly in the US, and 1:10,000 is the stated rate globally (Madhukark et al., 2016). There are specific groups of children that may be affected. Brazil is the country where a large number of cases of microcephaly occurred during the last several years. 3174 cases and 38 deaths were recorded in Brazil in 2015 (Madhukark et al., 2016). Certain congenital conditions may be the reason for the creation of an affected group. Children, whose mothers use alcohol or certain drugs before or during pregnancy, have infections like Zika virus or chickenpox, or are diagnosed with PKU (phenylketonuria), are exposed in the womb.
Etiology
Microcephaly can be genetic or caused by abnormal brain development. In some cases, this pathology may be the result of chromosomal abnormalities or the changes in genes that are hard to predict, observe, and treat (Liuzzi et al., 2016). Other known causes of microcephaly include a wrong function of centrosomes and the growth of the cerebral cortex. Infectious causes are the presence of such viruses as rubella, cytomegalovirus (CMV), and Zika (Liuzzi et al., 2016). The Zika virus has certain effects on the development of microcephaly in children. It may infect the fetus when a parent is exposed to the Zika virus and cause certain neurodevelopmental dysfunctions (Madhukark et al., 2016). The last cause has a direct correlation in the epidemiological data because it proves the chosen affected group that includes the children whose mothers have the Zika virus.
Affected Systems
The nervous system is the main system that is affected in patients with microcephaly (Liuzzi et al., 2016). This system is responsible for the transmission of nerve impulses through the body. When delays occur, homeostasis is developed, and new changes influence human development. Wrong brain work influences the work of the muscular system that is responsible for the skeletal muscles’ contractions (Woods & Basto, 2014). The endocrine system may be challenged because of hormone delays that participate in neural processes.
Normal vs. Abnormal Development
Brain tissue is affected by microcephaly. Not many children can survive with microcephaly caused by the presence of the Zika virus in the brain tissue. The brain is a central part of the nervous system. The development of the nervous system begins when the notochord turns ectoderm into a neuroectoderm that can be developed in a neural plate. The neural plate forms a neural groove that is lined by a neural fold on each side. The next stage in brain development is the formation of the neural tube. It is formed during the third week of gestation (Denny et al., 2013). By the end of gastrulation, two ridges form two neural folds that become one neural tube. The neural progenitor cells can be found between the ridges. Fusion o the neural folds is initiated at several places of the rostral-caudal axis (Stiles & Jernigan, 2010). After fusion, two continuous epithelial layers are formed. One is outer surface ectoderm, and another is a neural tube. Before the end of the fourth week of gestation, the caudal neuropore closes, and the neural tube is formed (Stiles & Jernigan, 2010). At the beginning of the neurulation process, the embryo is 3-5 mm long. At the end of the neural tube’s formation, the size of the embryo is 27-31 mm.
Figure 1: Morphological Changes of the Embryo (Stiles & Jernigan, 2010)
In Figure 1, there are several pictures that can be used as the fate-map of normal development of the neural tube in the embryo. A – the formation of the neural ridges, B – the beginning of the neural tube formation, C – the end of the neural tube formation. Microcephaly is the condition caused by unpredictable and uncontrollable neural stem cell proliferation during the embryonic development that may result in the death of neurons (Denny et al., 2013). The Zika virus, as the main contributor of microcephaly in fetuses, may infect an organism and kill the primary stem cells that have to be properly developed in the brain. The loss of any neuron leads other changes in head’s size and the development of human brain functions.
Treatment
The main threat of microcephaly is that no definite treatment can be offered to children. It is impossible to reverse complications or enlarge the size of child’s head. No direct treatment, but only alternative ideas should be discussed. The goal of any treatment is to manage child’s condition and support them and their families by any possible means, including speech and physical developmental therapies and occupational therapies which strengthen child’s abilities. Some medications and relaxing exercises can be offered to deal with hyperactivity if any.
Personal Interest
The fact that people cannot find out treatment for such pathology, it is interesting and challenging to observe the latest news and achievements on the chosen topic. The consideration of biological research and conferences can help to check on the latest changes and realize if microcephaly can be treated, and children can be saved. It is not fair that children should suffer from such birth defect as microcephaly, and it is necessary to do something to find the solution.
References
Denny, K.J., Jeanes, A., Fathe, K., Finnell, R.H., Taylor, S.M., & Woodruff, T.M. (2013). Neural tube defects, folate, and immune modulation. Birth Defect Research Part A: Clinical and Molecular Teratology, 97(9), 602-609.
Liuzzi, G., Puro, V., Vairo, F., Nicastri, E., Capobianchi, M.R., di Caro, A., … Ippolito, G. (2016). Zika virus and microcephaly: Is the correlation, causal or coincidental? New Microbiologica, 39(2), 83-85.
Madhukark, G.V., Bhaysaheb, D.K., Babasaheb, K.K., Tukaram, D.R., & Balkrishna, S.S. (2016). Zika virus infection: An overview. World Journal of Pharmacy and Pharmaceutical Science, 5(4), 2191-2204.
Stiles, J., & Jernigan, T.L. (2010). The basics of brain development. Neuropsychology Review, 20(4), 327-348.
Woods, C.G., & Basto, R. (2014). Microcephaly. Current Biology, 24(23), 1109-1111.
Nowadays, it became a commonplace trend among healthcare practitioners and biologists to refer to the explosive spread of Zika virus (ZIKV) that has taken place throughout the last decade; as such that represents an acute epidemiological threat to humanity. The reason for this apparent – as time goes on, there is being gathered more and more circumstantial evidence as to this virus’s capacity to trigger the development of physical deformities in human fetuses (microcephaly).
Moreover, ever since 2013, ZIKV has been increasingly reported in conjunction with people being diagnosed with Guillain-Barré syndrome – something that presupposes Zika’s ability to have a neurotropic effect on the functioning of one’s brain. What adds to the issue’s severity even more is that, as of today, there are no vaccines or antivirals specifically designed to inhibit Zika’s self-replication within the cells of a human body.
Partially, this can be explained by the fact that even today, many subtleties of the virus’ pathogenesis remain undiscovered – not the least because of Zika’s phylogenetic similarity with other flaviviruses, which makes its positive identification rather challenging (Paixao, Barreto, Teixeira, Costa, & Rodrigues, 2016). To complicate things even further, there is the apparent lack of Zika-related academic publications, which certainly does make sense, given the epidemic’s sheer recentness.
The latter observation, however, presupposes that at this stage of the ongoing research on Zika, it is thoroughly possible to derive a number of qualitative insights into the concerned subject matter by reviewing the available literature of relevance. This research paper aims to accomplish just that. In particular, the emphasis will be placed on outlining the possible strategies for reducing the risk of Zika being transmitted via blood transfusion, as elaborated upon by different authors. Readers will also be able to learn the main historical/epidemiological facts about the virus, as well as to find out what are the main obstacles on the way of health authorities from different countries trying to work out an effective approach for tackling the scope of potential dangers, posed by Zika.
Main part
Historical excurse
Zika is a virus, named after the Zika forest in Uganda, where it was documented for the first time in 1947. It has much in common with other flaviviruses, such as Dengue and Yellow Fever. People infected with Zika experience some general weakness and occasionally – a skin rash. The virus is spread by a certain kind of tropical mosquitoes, known as Aedes. Ever since it was discovered, Zika has been circulating around some parts of Africa and Asia, but it did not appear to be doing much damage to the exposed populations. Up to 80% of all infected individuals showed no symptoms, whatsoever (Gould & Solomon, 2008).
In the year 2007, the virus began to move eastwards – the development that caused the outbreak of Zika epidemic on the island of Yap in the Philippine Sea. However, not even a single instance of hospitalization was reported. In November of 2015, health officials in Brazil began to raise the alarm about a worrying trend – the dramatic increase in the number of children born with the condition of microcephaly (extremely small heads) in the country’s areas with the largest percentage of the registered Zika-cases.
Whereas, prior to the year 2015, there used to be no more than 400 microcephaly-birth cases reported in this country on an annual basis, by now the number of such cases has reached a staggering 5079 (Barton & Salvadori, 2016). Initially, there were only a few reasons for healthcare specialists in Brazil to suspect Zika of having been the actual culprit, in this respect. However, it did not take too long for Zika’s RNA to be found in the blood of women pregnant with defective babies.
As of today, it still remains unclear whether the Zika virus had anything to do with the dramatic upsurge of microcephaly in Brazil. However, as time goes on, more and more physicians throughout the world come to conclude that the virus and the incapacitating condition of microcephaly in children are indeed interrelated. On April 13, 2016, The Center for Disease Control and Prevention (CDC) officially declared Zika to be responsible for causing birth-defects (Baden, Petersen, Jamieson, Powers, & Honein, 2016).
As of now, there is still no vaccine in existence for this specific virus. Therefore, most recommendations as to how avoid being infected are concerned with encouraging people to exercise vigilance. Pregnant women are advised to refrain from visiting Zika-active countries in South America and Asia. Those already living there are instructed to avoid mosquito bites.
As of today, researchers are working to clear up many things about Zika that continue to remain a mystery. In this regard, the most crucial challenge is to find out whether this specific virus is capable of affecting the prenatal development of a fetus. Simultaneously, scientists continue to apply much effort into working out an effective strategy for keeping the virus well contained and preventing it from being able to gain any more ground. So far, there have been no significant breakthroughs, in this respect. One of the reason for this is that, as it moves across the planet, Zika continues to mutate – something that causes physicians a great deal of worry.
After all, it is not only that the virus appears fully capable of adapting to the unfamiliar climatic conditions, but it also exhibits a tendency to affect the workings of the infected people’s psyche. Therefore, the importance of studying Zika and its spatial characteristics cannot be overestimated.
Risk-reducing strategies
As it was mentioned earlier, Zika is a vector-borne virus, which implies that most people become infected due to being bitten by Aedes mosquitoes. Nevertheless, such a transmittance-route presupposes that there is also a certain possibility for this virus to find its way into a person’s body by the mean of a sexual intercourse and blood transfusion. The scenario’s plausibility can be illustrated, regarding the fact that the first incidence of Zika’s sexual transmission (in French Polynesia) was confirmed as far back, as in 2007, and also the fact throughout the year 2015, there were at least four confirmed episodes of Zika’s transfusion transmission having taken place in Brazil (Barjas-Castro et al., 2016).
Therefore, it does not come as a particular surprise that, as of today, many scientists/healthcare workers are concerned with trying to conceptualize the strategies for reducing the risk of transfusion transmission of Zika. Even though such their quest is still through its early phases, it is already possible to outline the would-be deployed approaches to addressing the task in question.
Probably the most logical/easily implementable of them is educating people about the potential danger of traveling to the areas where Zika has been known to proliferate (Ahmad, Amin, & Ustianowski, 2016). Although this particular suggestion does not seem to be directly related to the objective of reducing the likelihood for the virus to be transmitted to patients by physicians (during the blood transfusion procedure), this is far from being the actual case. The statement’s validity can be illustrated, with respect to the recorded (in 2015) instance of five tourists from Netherlands having been infected with the virus in Suriname, which they ended up carrying along back to Europe.
One of these tourists has been known as an active blood donor for most of his life (Goorhuis et al., 2016). Given the fact that the virus’s incubation period in the Netherlands proved to be as long as 28 days (in the tropical regions, this period rarely lasts for longer than 14 days), there is a good probability that, after having returned from the trip, the concerned individual did ‘succeed’ in passing the virus to more than one person.
The soundness of the educational approach to reducing the transfusion-related risk of Zika’s transmission will become particularly apparent in light of the earlier mentioned fact that due to the pandemic’s recentness, there still remains much uncertainty as to its etiology. Moreover, many people continue to disregard the prospect of being infected with Zika, because of their belief that the dangers posed by this particular virus are deliberately exaggerated by those who act on behalf of the pharmaceutical industry in the West (Martins, Dye, & Bavari, 2016).
Another strategy that is being commonly proposed for deployment, within the context of how physicians strive to diminish the discussed risk, has to do with the idea that donors should be screened for the presence of ZIKV RNA in their blood – especially if they reside in the areas with tropical/subtropical climate. What will come in particularly handy, in this respect, is that on March 30, 2016, Roche Molecular Systems introduced the first Zika NAT (nucleic acid test) assay for identifying the virus’s presence in donor blood (Lanteri et al., 2016).
It is understood, of course, that it will not be overnight that this assay becomes available in the Third World countries, affected by the pandemic the most. However, there can be only a few doubts that the development in question will contribute rather substantially towards ‘empowering’ humanity in its confrontation with Zika. Meanwhile, the World Health Organization (WHO) encourages donors to report whether they have had any Zika-like symptoms within the period of 14 days, prior to donating blood.
The main challenge, in this regard, is that there is very little specificity to the symptoms of one being infected with Zika – something that will inevitably undermine the effectiveness of self-reporting, on the part of donors (Basarab, Bowman, Aarons, & Cropley, 2016).
The latter consideration prompted the WHO to insist that the collection of donor blood should only be allowed to take place in the areas that have never been affected by the pandemic of Zika. Moreover, the organization’s representatives also call to enact the bylaw that would disqualify from being able to donate blood even those individuals who have stayed in the Zika-‘rich’ parts of the world for as little, as one day (Sikka et al., 2016).
The enactment of such a bylaw should come hand in hand with the application of a continual effort into helping people to increase their awareness of what may account for the possible consequences of one’s infestation with Zika, and what represent the most effective risk-avoidance strategies, in this respect. Because Zika has been confirmed sexually transmittable, the WHO suggests that no blood should be taken from those donors who are known to pursue a sexual relationship with active travelers to the Zika-infested areas for the duration of at least 28 days, after the last time that both parties have had sex (Kindhauser, Allen, Frank, Santhana, & Dye, 2016).
While scientists continue to study the virus so that it could be spatially contained, physicians are advised to resort to keeping blood components in quarantine, as yet another method of reducing the risk for patients to end up infected with Zika ‘by a needle’. The method’s practical implementation is concerned with freezing the would-be transfused blood materials and keeping them quarantined for a duration of at least 14-20 days – the timespan required for the symptoms of Zika to manifest in donors (Doshi, 2016).
Despite this method’s apparent simplicity, it has proven effective in the past. For example, it is now commonly assumed that one of the reasons why health authorities were able to put an end to the rapid spread of the West Nile virus during the nineties, is that they were quick enough to decide to quarantine donor blood in the affected areas. Given the pathogenic similarity between this particular virus and Zika, there can be very little doubt that the quarantining of blood components is indeed fully appropriate, as the instrument of preventing the latter from being transfusion-transmitted.
Unfortunately, there could be more obstacles on the way of implementing the earlier mentioned risk-reduction strategy than one may expect. The reason for this is that there is a high demand for donor blood all over the world. In most Western countries, the task of addressing this demand is largely delegated to the so-called ‘blood banks’ – the institutions that are being unofficially curated by the International Committee of the Red Cross (ICRC), which in turn has close ties with the Catholic Church.
This Church’s officials, however, have always been known for their strongly arrogant attitudes towards the prospect of relying on science, within the context of how a particular virus-triggered epidemic is being dealt with – the activities of Mother Theresa, who used to insist that there is no need to sterilize blood-transfusing needles, illustrate the validity of this statement (Hitchens, 2004). Because of this particular consideration, it will only be logical to assume that the initiative to quarantine blood components, as the mean of lowering the risk of Zika’s transmittance, will not prove very popular with health authorities – especially given the sheer power of the Catholic Church in the affected areas.
As it appears from the academic publications of relevance, there are also a few truly innovative techniques being developed to contain the spread of Zika by ensuring that this virus will not compromise the safety of blood transfusions. Probably the most notable of them is concerned with the idea of exposing frozen plasma and platelet concentrates to UVA (ultraviolet) light, in order to disable the virus’s function of self-replication. According to the empirically obtained findings of the 2016 study by Aubry, Richard, Green, Broult, and Musso, this idea is indeed thoroughly viable.
The reason for this is that while conducting their study, the authors were able to confirm that in the aftermath of having been treated with UVA, the infected (with Zika) substances had ceased indicating the presence of the targeted viral RNA. Given the fact that throughout the last few years the spread of Zika has gained nothing short of an exponential momentum, there can be only a few doubts as to the sheer importance of this study’s findings.
After all, once the proposed technique is being perfected, it will be possible to substantially reduce the risk of contracting the virus due to blood transfusion and even to eliminate it altogether. What is especially valuable about the solution in question, is that it is rather inexpensive, which makes it thoroughly suitable to be deployed in the Third World countries. At the same time, however, it is much too early to assume that the treatment of donor blood with ultraviolet light will prove 100% effective, as the virus-deactivating measure.
Conclusion
The main discursive insights of this research paper can be formulated as follows:
There is a good reason to believe that the pandemic spread of the Zika virus does have a strong effect on the epidemiological situation in the world. In its turn, this implies that a number of pro-active steps should be taken to minimize the affiliated threats.
The likelihood of Zika’s transmittance via blood transfusion can be reduced by taking advantage of quite a few time-tested strategies that have been designed to lessen the severity of viral hazards, faced by humanity. Among the best known of them, can be named: selective screening of blood donors, educating people about the dangers of Zika, delegitimizing the collection of donor blood from those who reside in the affected regions, quarantining blood materials, and deactivating Zika’s self-replicating code.
There are both: advantages and disadvantages to each of the outlined strategies for reducing the risk of Zika’s transmittance. In its turn, this implies that the practical deployment of these strategies should be circumstantially appropriate.
Along with the purely technical aspects to the question of what should be done to ensure that blood transfusions remain ‘Zika-free’, there are some societal ones, as well.
It would be intellectually dishonest to claim that this research paper contains many of the previously unexplored acumens into the discussed subject matter. However, there is a good rationale to believe that will prove useful to those interested in finding out more about Zika, in general, and about what can be done to make sure that blood transfusions do not result in the virus’s transmittance, in particular. Because of the paper’s size-wise format, its findings cannot be deemed exhaustive. Therefore, it can be recommended that while conducting research on the same/similar topic in the future, researchers should focus on identifying the link between the spatial features of Zika’s pandemic, on one hand, and the discursive essence of social dynamics in the affected areas, on the other.
References
Ahmad, S., Amin, T., & Ustianowski, A. (2016). Zika virus: Management of infection and risk. BMJ : British Medical Journal, 352, 1-5.
Aubry, M., Richard, V., Green, J., Broult, J., & Musso, D. (2016). Inactivation of Zika virus in plasma with amotosalen and ultraviolet A illumination. Transfusion, 56(1), 33-40.
Baden, L., Petersen, L., Jamieson, D., Powers, A., & Honein, M. (2016). Zika virus. The New England Journal of Medicine, 374(16), 1552-1563.
Barjas-Castro, M., Angerami, R., Cunha, M., Suzuki, A., Nogueira, J., Rocco, I., &… Addas-Carvalho, M. (2016). Probable transfusion-transmitted Zika virus in Brazil. Transfusion, 56(7), 1684-1688.
Barton, M. & Salvadori, M. (2016). Zika virus and microcephaly. Canadian Medical Association Journal, 188(7), E118-E119.
Basarab, M., Bowman, C., Aarons, E., & Cropley, I. (2016). Zika virus. BMJ : British Medical Journal, 352, 1-7.
Doshi, P. (2016). Convicting zika. BMJ: British Medical Journal, 353, 1-3. Goorhuis, A., von Eije, K., Douma, R., Rijnberg, N., van Vugt, M., Stijnis, C., &
Grobusch, M. (2016). Zika virus and the risk of imported infection in returned travelers: Implications for clinical care. Travel Medicine and Infectious Disease, 14(1), 13-15.
Gould, E., & Solomon, T. (2008). Pathogenic flaviviruses. The Lancet, 371(9611), 500-509.
Hitchens, C. (2004). Less than Miraculous. Free Inquiry, 24(2), 14-18.
Kindhauser, M., Allen, T., Frank, V., Santhana, R., & Dye, C. (2016). Zika: The origin and spread of a mosquito-borne virus. World Health Organization: Bulletin of the World Health Organization, 94(9), 675-686.
Lanteri, M., Kleinman, S., Glynn, S., Musso, D., Hoots, W., Custer, B., &… Busch, M. (2016). Zika virus: A new threat to the safety of the blood supply with worldwide impact and implications. Transfusion, 56(7), 1907-1914.
Martins, K., Dye, J., & Bavari, S. (2016). Considerations for the development of Zika virus vaccines. Vaccine, 34(33), 3711-3712.
Paixao, E., Barreto, F., Teixeira, M., Costa, M., & Rodrigues, L. (2016). History, epidemiology, and clinical manifestations of Zika: A systematic review. American Journal of Public Health, 106(4), 606-612.
Sikka, V., Chattu, V., Popli, R., Galwankar, S., Kelkar, D., Sawicki, S.,… Papadimos, T. (2016). The emergence of Zika virus as a global health security threat: A review and a consensus statement of the INDUSEM joint working group (JWG). Journal of Global Infectious Diseases, 8(1), 3-15.