The recent observed link between the Zika virus and neurodevelopmental disorders in Latin America has forced the world health organisation to place the outbreak as a public health emergency. So what is Zika and what are its effects on the nervous system?
The first reported infection from the Zika virus occurred in Uganda in 1947. Although the virus does show a wide geographical distribution, the outbreaks remained small and narrowly distributed until 2007 when there was a large epidemic, effecting 75% of the population on Yap Island. Zika, a mosquito-borne virus, belongs to the Flaviviridae family, which also includes the virus yellow fever. The species of Mosquito thought to be the main vector of the virus in South and South East Asia is the Aedes aegypti (Yssel et al., 2015). Studies have shown that there is a widespread distribution in North Africa as well as countries in Southeast Asia, including India and the Phillipines. These large outbreaks are characterised by mild flu like symptoms such as fever, rash, arthralgia, muscle and joint pain, malaise, headache and conjunctivitis (Yssel et al., 2015). Recent reports have suggested that the virus can also be spread through sexual transmission, however only two reported cases suggest this, and so the main focus of research remains on transmission via mosquito bite. The Zika virus is particularly a concern for pregnant mothers who are infected with the virus, as it can give rise to microcephaly.
Approximately 3 million babies are born in Brazil every year. In a normal scenario an estimated 150 babies would be diagnosed with microcephaly, whereas now Brazil are said to be investigating around 4000 cases. Many post mortems of infants who died with microcephaly have been shown to present the Zika virus within their brains, and it has also been detected in the placenta and amniotic fluid.
Microcephaly is a disorder that affects neurological development. New-borns with the disorder tend to have smaller than average intracranial brain volume. There are two main types of microcephaly; primary microcephaly: when the brain is smaller at birth, and secondary microcephaly: when the brain is of normal size at birth but there is failure of the brain to develop normally post-natal (Woods 2004). The face develops at a normal rate which leads to an infant with a receding hair line and in many cases a wrinkled scalp. The cerebral cortex is particularly reduced which leads to a simplified gyral pattern and MRI studies have shown the frontal lobes to be particularly affected. Primary microcephaly is thought to be caused by a decrease in neurones produced by neurogenesis, whereas secondary microcephaly is characterised by a reduced amount of dendritic endings and synaptic connections (Woods,2004). Primary usually occurs before 32 weeks of gestation. The majority of neurones are formed by week 21 of foetal development, whereas dendritic connections and myelination mainly occur after birth; this explains the differences in the two variations of the disorder. Abnormalities are not just seen in regards to the brain and skull, later in life the body is usually seen to be underweight and dwarfed. Seizures severely impair intellectual development and disturbances in motor functions may also develop later due to the demyelination and reduced connectivity.
It is important to note that genetic factors, alcohol consumption of the mother during the pregnancy, maternal syphilis infections and poor pre-natal care can all be the cause of microcephaly. Thus further investigations are required to determine whether this causal link between Zika infection and microcephaly is directly related.
The infection is also thought to affect adults, resulting in temporary paralysis known as Guillain- Barré syndrome.
(Kaneshiro and Black, 2013)
Guillain- Barré syndrome
During the recent outbreak in French Polynesia (2013 and 2015) the reports of individuals with Guillain- Barré syndrome (GBS) increased 20-fold (Yssel et al., 2015). GBS is a disorder in which the immune system begins to attack part of the peripheral nervous system. These immune cells begin to destroy the myelin sheath and in some cases the axons also. When demyelination occurs the speed of electrical transmission is greatly reduced. This causes problems with both motor and sensory transmission, as the limbs receive and transmit information over longer distances, and thus are more susceptible to the adverse effects of demyelination. Initial symptoms of the disorder include myasthenia (weakness) and tingling sensations known as paraesthesia in the lower limbs. These go on to spread to the upper limbs. Because there is reduced sensory afferent feedback the individual becomes unable to detect and respond to mechanical, thermal and nociceptive stimuli efficiently. These effects increase in intensity until the point of paralysis, where specific muscles can no longer be used. If this syndrome progresses then there is a high risk of mortality as the paralysis can affect respiratory muscles and the cardiovascular system. Research suggests that when a virus like Zika causes this syndrome it may be due to the virus changing the cells of the nervous system In such a way that the immune system begins to recognise them as foreign, or removes the ability of the immune system to distinguish between its own cells and those that are foreign. This leads to immune cells such as macrophages phagocytosing and destroying cells of the peripheral nervous system, particularly the Schwann cells, which lay the myelin sheath.
Prognosis for the disease is fairly good: most individuals recover fully with only a few (around 30%) suffering from prolonged weakness. This may pose the question as to why there is such a panic over the Zika outbreak. However, regions where there is the highest number of cases do not have efficient access to healthcare, and therefore there is an increased risk of mortality, which must be considered.
Brazilian authorities are currently investigation other potential causes of microcephaly, but it seems that there is an increasing amount of evidence linking the virus with these disorders. The greatest problem is that 80% of Zika cases are asymptomatic; therefore pregnant women may not be aware that they’ve even contracted the infection. If there is a confirmed link between the virus and microcephaly, then research developments are required that enable efficient and prompt diagnosis, in addition to preventing the disease infecting pregnant women and those of childbearing age in the first place.
Kaneshiro, N.K. and Black, B. (2013) Microcephaly: MedlinePlus medical encyclopedia image. Available at: https://www.nlm.nih.gov/medlineplus/ency/imagepages/17256.htm (Accessed: 8 February 2016).
Woods, C.G. (2004) ‘Human microcephaly’, Current Opinion in Neurobiology, 14(1), pp. 112–117. doi: 10.1016/j.conb.2004.01.003
Yssel, H., Dejarnac, O., Wichit, S., Ekchariyawat, P., Neyret, A., Natthanej, L., Perera-Lecoin, M., Hamel, R., Talignani, L., Thomas, F., Cao-Lormeau, V.-M., Choumet, V., Briant, L., Desprès, P., Amara, A., Surasombatpattana, P., Missé, D., (2015) ‘biology of zika virus infection in human skin cells’, Journal of Virology, pp. 15–354.
Article by: Kate Pearman
Edited by Molly Campbell