Zika Virus Infection: Current Concerns and Perspectives

Clinic Rev Allerg Immunol (2016) 51:383–394 DOI 10.1007/s12016-016-8554-7 Zika Virus Infection: Current Concerns and Perspectives Mari Kannan Maharajan 1 & Aruna Ranjan 1 & Jian Feng Chu 1 & Wei Lim Foo 1 & Zhi Xin Chai 1 & Eileen YinYien Lau 1 & Heuy Mien Ye 1 & Xi Jin Theam 1 & Yen Ling Lok 1 Published online: 28 May 2016 # Springer Science+Business Media New York 2016 Abstract The Zika virus outbreaks highlight the growing importance need for a reliable, specific and rapid diagnostic device to detect Zika virus, as it is often recognized as a mild disease without being identified. Many Zika virus infection cases have been misdiagnosed or underreported because of the non-specific clinical presentation. The aim of this review was to provide a critical and comprehensive overview of the published peer‐reviewed evidence related to clinical presentations, various diagnostic methods and modes of transmission of Zika virus infection, as well as potential therapeutic targets to combat microcephaly. Zika virus is mainly transmitted through bites from Aedes aegypti mosquito. It can also be transmitted through blood, perinatally and sexually. Pregnant women are advised to postpone or avoid travelling to areas where active Zika virus transmission is reported, as this infection is directly linked to foetal microcephaly. Due to the high prevalence of Guillain-Barre syndrome and microcephaly in the endemic area, it is vital to confirm the diagnosis of Zika virus. Zika virus infection had been declared as a public health emergency and of international concern by the World Health Organisation. Governments and agencies should play an important role in terms of investing time and resources to fundamentally understand this infection so that a vaccine can be developed besides raising awareness. * Mari Kannan Maharajan ; 1 Department of Pharmacy Practice, School of Pharmacy, International Medical University, Kuala Lumpur 57000, Malaysia Keywords Zika virus . Diagnosis . Cytokines . Transmission . Management Introduction Recent international media attention has focused on microcephaly, which is a potential neurological and immunological complication. Clinical and epidemiological reports showed that there is a link between microcephaly and of Zika virus (ZIKV). ZIKV is a mosquito-borne disease transmissible from human to human through bites of Aedes species. The genome of the ZIKV, of Flaviviridae family and of the Flavivirus genus [1] is a single positive-strand RNA closely related to Spondweni virus [2, 3]. ZIKV was initially distinguished in rhesus monkeys in the Zika forest of Uganda throughout the period of a yellow fever study [3]. Despite its first isolation 6 decades ago, little attention has been given to ZIKV compared with the other mosquito-borne flaviviruses. Only 14 cases of human ZIKV infection had been recognized globally, and no outbreak had been reported until 2007, when ZIKV spread further to the Pacific Island of Yap [4, 5]. This was the first outbreak reported beyond the confines of Africa and Asia [4, 6]. The second and largest outbreak occurred in French Polynesia [7, 8]. With 383 confirmed cases, it is estimated that ZIKV disease may be the reason why approximately 32,000 patients sought medical care between October 2013 and April 2014 [9]. It has only come to international attention recently after the outbreak on Yap Island in 2007 and the current epidemic on Brazil in 2015 [10]. Indigenous dissemination of ZIKV has been detected, as ZIKV infection has been confirmed in 18 states of Brazil [9]. The geographical distribution of ZIKV has steadily broadened given the wide distribution of the mosquito vector. ZIKV infection has been spotted in the USA territories of Puerto 384 Clinic Rev Allerg Immunol (2016) 51:383–394 Fig. 1 All countries and territories with active Zika virus transmission. As of May 5, 2016, retrieved from Centers for Disease Control and Prevention. http://www.cdc.gov/zika/geo/active-countries.html Rico, the US Virgin Islands and American Samoa [11–13]. Although mosquito-borne transmission of ZIKV infection has not been reported yet in continental USA, cases of imported ZIKV infection have been reported in pregnant and non-pregnant travellers [14–16]. Figure 1 shows all countries and territories with active ZIKV transmission. This has negatively impacted the safety of other regions, putting them at greater risk, as there is a greater connectivity between the continents as a result of millions of international travellers across the globe. Between 2007 and 2016, 66 countries and territories reported ZIKV transmission. Since 2015, 42 countries are experiencing their first outbreak of ZIKV, with no previous evidence of circulation, and with on-going transmission by mosquitos. Other than a mosquito-borne transmission, eight countries (Argentina, Chile, France, Italy, New Zealand, Peru, Portugal and the United States of America) have reported evidence of person-to-person 1952 Uganda 1969-1983 Asia (India, Indonesia, Thailand and Pakistan) 2007 Pacific sland of Yap Fig. 2 Global spread of the Zika virus 2013-2014 French Polynesia, Easter Island, Cook Islands, New Caledonia 2015-Apr 2016 Brazil, Columbia, United States, Vennezula, Maldieves transmission of ZIKV [17]. Upon scrutinizing the cases reported worldwide, the Central and South American countries could be the most burdened by ZIKV outbreak, because the estimated number of cases reported was around 440,000 to 1, 300,000, which is much higher than that in other countries [18, 19]. The prospect of ZIKV spreading across regions and continents, along with neurological disorders can be anticipated from the recent outbreaks [20]. Figure 2 summarizes the timeline of global spread of ZIKV infection Clinical Presentation The manifestation of human ZIKV infection ranges from asymptomatic to influenza-like symptoms. Clinical manifestations of infection include fever, headache, retro-orbital pain, arthralgia, asthenia, malaise, myalgia, anorexia, rash, oedema, lymphadenopathy and diarrhoea; in most cases, the infection appeared mild and self-limiting, with a mean symptom duration of 3–6 days [21, 22]. Conjunctivitis is commonly present, whereas arthralgia, headache, and malaise are less prominent. Shock complications and haemorrhagic signs have not been reported. However, Guillain-Barre syndrome, a neurologic complication, was reported in French Polynesia [23]. Laboratory tests revealed transient leukopenia and Clinic Rev Allerg Immunol (2016) 51:383–394 thrombocytopenia. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) concentrations may or may not be raised [10]. In 2008, Foy et al. reported two unusual cases of ZIKV infection presenting with aphthous ulcers, prostatitis and hematospermia which are not common [24]. ZIKV infection has been regarded as benign in most cases until the Brazil Ministry of Health considered a link between the ZIKV infection and microce (...truncated)