INTRODUCTION:

The explosive outbreak of zika virus and the clinical deformity caused, has taken world by storm. Inspite of medical advancements and improvement in clinical research, each year, sudden infections emerge and surface posing problems for the health workers and placing researchers at a challenging platform, to develop, protect, treat and save the needful from such threats. In recent years, a number of arthropod-borne viruses (arboviruses) have emerged or re-emerged as west nile virus, dengue virus or chikungunya virus.¹ And out of all these, Zika virus has been given much importance due to the deformaties it can cause in humans and according to the recent reports it can also be sexually transmitted.^2,3

DATA SOURCES AND RESOURCE SELECTION:

Articles published on Zika virus in indexed and non-indexed journals in electronic database (MedLine, Pubmed, Embase) news and research based scientific forum were evaluated and the ones suited the authors’s requirement have been referenced. Articles published on ZIKV so far, discuss it’s clinical manifestations and neurological anomalies caused by the virus. However, as the research indicates, Zika virus has evolved with time and has been causing severe problems there is a possibility that virus might show various dental manifestations or clinical problems in any other part of the body in future. Keeping this into consideration, according to authors’s knowledge, this is the first article which discusses possible role of Zika virus in causing Medical and Dental diseases.

REVIEW:

Historical background so far:

Zika virus (ZIKV) is new to the modern world, however the occurrence of Zika can be traced back to 1947 when it was first identified in the Rehseus monkey⁴ in a forest named Zika, from where the virus takes its name. The Zika forest is located in Uganda, which attracts many researchers each year to study viruses and mosquitoes which act as carriers.⁴ On one such occasion in 1947, Zika was discovered by Alexander Haddow and colleague George Dick while studying yellow fever,⁵ and was recovered from the mosquito Aedes africanus in 1948 caught on a tree platform.^5,6 The first few human cases of Zika were detected in 1952 in Uganda and the United Republic of Tanzania in a study demonstrating the presence of neutralizing antibodies to Zika virus in sera.⁷ In 1954, the virus could be isolated from a young girl in Eastern Nigeria during an epidemic of jaundice.⁸ In 1964 the virus was isolated and re-isolated by a researcher in Uganda who himself got infected with Zika strains, and proved for the first time that humans could be infected with Zika virus.⁹ He also reported that the disease is of ‘mild nature’ and that “it is not surprising under normal circumstances the virus is not isolated frequently from man”.⁹

With time, serosurvey studies could detect ZIKV antibodies conducted in various parts of the world including Africa^10-12and Asia.^13,14 And by 1983, geographical distribution of Zika was marked which expanded to parts of Asia, including countries like Malaysia, Indonesia, Pakistan and India, where mosquito was the main carrier of the virus.^15-18 Researchers later suggested that the clinical signs and symptoms of Zika infection match with that of dengue and chikungunya, as a result the disease was not known or reported rarely in Asia.¹⁹ Since its discovery, the virus has been causing occasional human infections in these two continents, until 2007 when its epidemic first emerged in Yap Island,²⁰ and as they say rest is history, ZIKV in 2013, caused a large epidemic in French Polynesia, concomitant with a dengue epidemic²¹ and has been considered as emergent since 2007.^22,23

The virus and transmission:

ZIKV is an enveloped, icosahedral, arbovirus of the family Flaviviridae, genus Flavivirus²⁴ as dengue, yellow fever, Japanese encephalitis, West Nile, and Saint-Louis encephalitis viruses.²⁵ It is phylogenetically and antigenically related to the Spondweni virus and is a single-stranded RNA virus.²⁶ It is a mosquito-borne flavivirus and vectors from Aedes genus and monkeys are required by the virus for its transmission, whereas humans are occasional hosts²⁷ and occur when an infected female mosquito bites a human. There are two main lineages of Zika virus, the African lineage and the Asian lineage,²⁸ but some researchers suggest three and divide African lineage into two- West and East.²⁹ Reports have suggested that the Asian lineage is expanding which is responsible for the outbreaks in the Pacific²²and in South America.²¹

As it is an arbovirus, the transmission first occurs through the infected mosquito bite, however recent reports suggest the virus can also be transmitted sexually,³ perinatal and transplacental transmission during child birth⁴ and through blood transfusion. Diseases such as West Nile, Dengue, Chikungunya, and Zika infect to such an extent that viraemia remain constant and humans can become the primary vertebrate hosts in urban settings.³⁰ Detailed studies by Faye et al²⁷ showed that the virus has evolved since its discovery, which is uncommon among flaviviruses³¹ causing mild symptoms till its sudden outbreak since 2007^22,23and severe form of neurological disorders. Musso et al³ detected presence of high ZIKV RNA and replicative ZIKV in semen samples of infected patient, but at the same time, it remained undetectable in blood samples by rRT-PCR. Authors suggested that site of viral replication may have been the genital tract, however, questions like when it started and for how long remained unanswered.³

Symptoms:

ZIKV causes mild symptoms in humans which last for 15-21 days.²¹ ZIKV causes dengue-like symptoms in patients which include oedema of extremities, arthralgia, mild fever, maculopapular rashes²¹ starting from the trunk or face and later become more diffuse,^32,33 frequent pruritic, headaches, no purulent conjunctivitis, retroorbital pain, vertigo, myalgia and digestive disorder,²¹ photophobia, and other common symptoms such as cough, sore throat, aphtous ulcers, sweating and lymphadenopathies also occur.³⁴ Asthenia, post-infection happens to be a frequent symptom.^9,20,35 Zanluca et al²¹ reported the first case of Zika virus in Brazil stated that most common symptoms were maculopapular rashes and joint pains occurring in hands, ankle, elbow, knee, wrist, foot and also cervical pain. Authors also reported that most of the patients had normal levels of leukocytes, neutrophils and platelets.²¹

Another important symptom observed in patients in recent outbreaks was the severe neurological complication known as, Guillain-Barré syndrome (GBS) having a 20-fold higher incidence than usually observed.^23,25,36 It shows acute and flexic paralysis with albuminocytologic dissociation and is at present, the most common cause of acute flaccid paralysis worldwide considered as one of the serious emergencies in neurology.³⁷ Symptoms include paresthesia, numbness, weakness and pain in the limbs.³⁷ Same features were observed by Oehler et al²⁵ and reported the first case of GBS developed after seven days of Zika infection and hospitalization due to worsening of the condition. Diagnosis was based on IgM/IgG serological results and plaque reduction neutralization test (PNRT).

Yet another reason why the world is worried about its spread is the fetal brain deformity or microcephaly, caused by Zika infection. By November 2015, the number had rapidly increased to 646 cases in Pernambuco state alone in relation to microcephaly caused by Zika infection which making Brazilian ministry of health to declare it as a public health emergency.³⁸ Oliveira et al³⁸ reported fetal brain injury, retardation in brain growth and presence of ZIKV in amniotic fluid in two cases who developed microcephaly, which was consistent with intrauterine transmission of the virus. Mlakar et al³⁹ also reported a similar case where, CNS was severely affected causing gross intrauterine growth retardation and placenta damage by the virus. Authors also suggested a strong neurotropism of the virus which was confirmed on electron microscopic evaluation.³⁹

POSSIBLE DENTAL RELATION WITH ZIKA VIRUS:

Occurrence of apthae ulcers³⁴ is one of the clinical manifestations of ZIKV, which has been occurring since the disease was first noticed in man and no other clinical manifestation in relation to dentistry has been noted so far. But as the virulence has grown stronger with time and has shown capability to adapt to its new environment³⁹ there is a possibility that virus might show various dental manifestations or clinical problems in any other part of the body. Since Zika’s evolved strain²⁷ has started infecting fetus and forming microcephaly,^38,39 it has become a matter of concern to control the disease. Oral manifestations of newly evolved Zika virus are not known yet, except that it causes microcephaly which can lead to several other dental problems.

Microcephaly is a part of more than 450 syndromes,⁴⁰ in Zika related microcephaly no occurrence of any syndrome has been reported so far, nonetheless, patients will have the following dental problems pertaining to microcephaly:

· Developmental delays⁴⁰ such as speech, difficulty in swallowing and feeding.^41,42

· Mental retardation⁴¹ causing difficulty in understanding, leading to oral hygiene related problems such as high caries index and periodontal problems due to plaque deposition.

· There will be facial distortions, which can lead to sinus related problems leading to problems such as anterior open bite and high arched palate.^41,42

· Such patients will have seizures⁴¹ and gingival enlargement related to its treatment.

· Teeth eruption cycle will be disturbed and shape of teeth altered.⁴¹

· Development problems related to maxilla and mandible may also be encountered which may lead to malocclusion.

· Might have enamel hypoplasia.

· Other problems encountered might be angular cheilitis, tongue thrust, bruxism.^41,43

Another unfortunate clinical manifestation is the development of cancer⁴⁴ in such patients which gets worsened due to lack of proper treatment due to physiologic limitations that these patients suffer. Enomoto et al⁴⁴ repotted a case of tongue cancer in patients suffering from microcephaly and stated that the incidence of cancer in such patients occurs as frequent as in the general population but oral cancer has slightly reduced incidence as there are only 11 cases reported in past 30 years.

Another role played by the oral cavity is in the diagnosis of Zika virus. Musso et al⁴⁵ stated that saliva can be used for the diagnosis of ZIKV in cases when collection of blood becomes difficult as ability to detect ZIKV RNA in saliva is higher as compared to blood. Also, ZIKV is positive in saliva during the acute phase of the disease while negative in blood.⁴⁵ However, as the authors state that saliva cannot replace blood samples, it should be used as an alternative diagnostic tool.⁴⁵

DISCUSSION:

It is clear from the aforementioned symptoms that Zika infection, till its epidemic used to cause mild symptoms, which were easily ignored many people and supportive treatment was given to the patient. However, since 2007 severe outbreaks^22,23have become evident caused by the evolved strain²⁷ of the same virus, causing fetal brain deformities,³⁸ making governments to take grave steps and declare public health emergency³⁸ and asking women not to get pregnant. But is the mosquito bite the only mode of transmission? According to Petersen et al⁴⁶ more than 130 arboviruses causing human disease are able to transmit virus through blood transfusion. Zika is one of them, which remains undetected in blood during the acute conditions, ⁴⁵ increasing the risk of blood transfusion safety. Apart from that, transmission through placenta and sexual transmission has also been reported which opens up a wide area of worry and ZIKV’s demographic and evolutionary potential.

The arbovirus, caused in humans by mosquito bite has evolved with time which is unusual among flaviviruses³¹ challenges our understanding of the virus. The virus has gone beyond its usual disease forming capacity, affecting adults and fetus causing neurological problems, out of which microcephaly remains a grave concern. Microcephaly then can cause developmental disorders affecting the oro-facial region. However so far, no syndrome has been related to ZIKV or it directly does not cause any dental problem other than apthous ulcer, which is not a serious concern, but can affect an individual through microcephaly. Such patients also demonstrate mental retardation and any dental disease in such patients becomes difficult to treat in many aspects.

What can be done to stop Zika from spreading? It is impossible to eradicate the mosquito Aedes aegypti which is found in wide tropical zone and has been causing diseases like dengue, yellow fever, Japanese encephalitis, West Nile, and Saint-Louis encephalitis.²⁵ The infected mosquito bites in the daytime, so precaution is the only treatment left. At home, or while going out, insect repellant should be applied to exposed body parts, houses should be kept clean and any container, old tires in the house should be discarded or pot-holes near the house should be taken care of. Water in the gardens should not be left stagnant. Communities should be kept clean, and apart from government each individual should make efforts to keep the surroundings hygienic so that mosquitoes do not breed. Education regarding the same to students at every level is necessary. Travelling to such countries should be avoided, as sexual transmission of the disease has also been reported.

CONCLUSION:

Zika has recently become known to the modern world due to its explosive outbreak and has shown that it is capable of causing much more than isolated cases²⁶ causing deformities such as fetal microcephaly making governments to declare a medical emergency. There are still many aspects of the disease such as the evolution of the virus, further possible symptoms and most importantly treatment of the disease that still remain unknown. However many of the symptoms can be linked to microcephaly, like dental which have already been aforementioned. Further research is required in understanding of the virus, its treatment such as developing a vaccine and efforts by the national health authorities in proper screening and reporting of the disease especially in the tropical countries where the disease is known since long.

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Received on 13.05.2019 Modified on 10.06.2019

Research J. Pharm. and Tech 2020; 13(9):4464-4468.

DOI: 10.5958/0974-360X.2020.00788.X