Pathogenesis, diagnostic challenges and treatment of zika virus disease in resource-limited settings.
01 Apr 2018-The Nigerian postgraduate medical journal (Medknow Publications)-Vol. 25, Iss: 2, pp 67-72
TL;DR: There is no routine laboratory diagnosis of ZIKV infection in resource-constrained countries, and serologic tests should be interpreted with caution since there can be cross-reactivity with other flaviviruses, especially in Africa where the burden of infection with flavivirus is comparatively high.
Abstract: The association of Zika virus (ZIKV) infection with congenital malformation and neurological sequelae has brought significant global concern. Consequently, the World Health Organization (WHO) declared it "a public health emergency of International concern" on 1 February, 2016. A critical review of its pathogenesis would lead to a better understanding of the clinical features and the neurological complications. This review is based on literature search in PubMed/Medline, Google Scholar and the WHO, http://www.who.int. This include all relevant articles written in English published through June 2018, with subject heading and keywords such as Zika, ZIKV, Zika pathogenesis, diagnosis of Zika, Zika Nigeria, Zika Africa and Zika resource-limited settings. Following ZIKV infection, viraemia ensues targeting primarily the monocytes for both the Asian and African strains. ZIKV infection by an African strain appears to be more pathogenic, in early pregnancy tends to result in spontaneous abortion. Whereas an Asian strain tends to be less pathogenic and more chronic, this allows the pregnancy to continue, ultimately resulting in congenital malformations. There is no routine laboratory diagnosis of ZIKV infection in resource-constrained countries. Serologic tests should be interpreted with caution since there can be cross-reactivity with other flaviviruses, especially in Africa where the burden of infection with flaviviruses is comparatively high. There is a paucity of well-equipped laboratories for comprehensive ZIKV diagnosis. It is imperative to strengthen the health systems, improve health workforce and diagnostic capacity of such settings.
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TL;DR: A new drug lead, pep14-23 (WO2008/028939A1), was designed and patented and it was demonstrated that it inhibits the interaction of DENV C protein with the host lipid system, a process essential for viral replication.
Abstract: Dengue virus (DENV), which can lead to fatal hemorrhagic fever, affects 390 million people worldwide. The closely related Zika virus (ZIKV) causes microcephaly in newborns and Guillain-Barre syndrome in adults. Both viruses are mostly transmitted by Aedes albopictus and Aedes aegypti mosquitoes, which, due to globalization of trade and travel alongside climate change, are spreading worldwide, paving the way to DENV and ZIKV transmission and the occurrence of new epidemics. Local outbreaks have already occurred in temperate climates, even in Europe. As there are no specific treatments, these viruses are an international public health concern. Here, we analyze and discuss DENV and ZIKV outbreaks history, clinical and pathogenesis features, and modes of transmission, supplementing with information on advances on potential therapies and restraining measures. Taking advantage of the knowledge of the structure and biological function of the capsid (C) protein, a relatively conserved protein among flaviviruses, within a genus that includes DENV and ZIKV, we designed and patented a new drug lead, pep14-23 (WO2008/028939A1). It was demonstrated that it inhibits the interaction of DENV C protein with the host lipid system, a process essential for viral replication. Such an approach can be used to develop new therapies for related viruses, such as ZIKV.
33 citations
TL;DR: This review focuses on cross-reactive T cell responses to flaviviruses and the concepts and consequences of T cellCross-reactivity, with particular emphasis linking data generated using murine models to the new understanding of disease outcomes following heterologous flavivirus infection.
Abstract: Most of the world is at risk of being infected with a flavivirus such as dengue virus, West Nile virus, yellow fever virus, Japanese encephalitis virus, tick-borne encephalitis virus, and Zika virus, significantly impacting millions of lives. Importantly, many of these genetically similar viruses co-circulate within the same geographic regions, making it likely for individuals living in areas of high flavivirus endemicity to be infected with multiple flaviviruses during their lifetime. Following a flavivirus infection, a robust virus-specific T cell response is generated and the memory recall of this response has been demonstrated to provide long-lasting immunity, protecting against reinfection with the same pathogen. However, multiple studies have shown that this flavivirus specific T cell response can be cross-reactive and active during heterologous flavivirus infection, leading to the question: How does immunity to one flavivirus shape immunity to the next, and how does this impact disease? It has been proposed that in some cases unfavorable disease outcomes may be caused by lower avidity cross-reactive memory T cells generated during a primary flavivirus infection that preferentially expand during a secondary heterologous infection and function sub optimally against the new pathogen. While in other cases, these cross-reactive cells still have the potential to facilitate cross-protection. In this review, we focus on cross-reactive T cell responses to flaviviruses and the concepts and consequences of T cell cross-reactivity, with particular emphasis linking data generated using murine models to our new understanding of disease outcomes following heterologous flavivirus infection.
15 citations
TL;DR: The present review emphasizes various features of ZIKV and its history, epidemiology, transmission, clinical manifestations, progress and advances in developing effective diagnostics, vaccines and drugs/therapeutics along with accepting suitable avoidance and control strategies to undertake this deadly emerging disease.
Abstract: The mosquito-borne arbovirus Zika virus (positive-stranded RNA virus, ZIKV, Flavivirus, Flaviviridae), has caused an outbreak imposing by its extent and quick spread. This became the focus of a current pandemic and public health crisis all around the world because of the incessant geographic growth of both the virus and its mosquito vectors; it is often misdiagnosed with other disease like yellow fever, west nile, dengue and chikungunya because of same clinical manifestation. After unprecedented huge scale outbreak of ZIKV in Pacific, Micronesian island of Yap in 2007, though ZIKV infections are in general sporadic cases or causing mild self-limiting illness, harsh symptoms have been explained including neurological disorders, autoimmune disorder, fetal anomalies, impaired central nervous system of the fetus, microcephaly in newborns, meningoencephalitis, myelitis and Guillain Barre´Syndrome supposed to be linked with ZIKV. The virus is transmitted mainly by a mosquito Aedes aegypti, whereas, other routes of viral broadcast includes monkey bite, coitus and body fluids such as semen, blood and saliva which needs further corroboration. The relationship between these conditions with ZIKV infection is still not established and is under assessment. Till now there is no vaccine or specific antiviral against ZIKV, therefore the public health authority focuses on preventing infection, mainly in pregnant women and virus transmitted area. WHO and other health officials are working on the expansion of new projects and mosquito control techniques to manage up with infection as there is very fewer literature present on the pathogenesis of the ZIKV to help understand the clinical disease spectrum and target treatments to decrease or stop infection. The future status of ZIKV dispersal to other parts of the world is still unknown. The present review emphasizes various features of ZIKV and its history, epidemiology, transmission, clinical manifestations, progress and advances in developing effective diagnostics, vaccines and drugs/therapeutics along with accepting suitable avoidance and control strategies to undertake this deadly emerging disease.
Keywords: Zika virus, Flavivirus, Aedes aegypti, Pregnancy, Transmission, Microcephaly, Africa
6 citations
TL;DR: The need to improve surveillance mechanisms and focusing on vector control as critical steps to enable prompt detection and avert potential outbreaks of the disease in the continent is identified.
Abstract: Zika virus (ZIKV) that was less known for decades suddenly became a global health emergency at the beginning of 2016. The virus was first discovered in the Zika forest of Uganda in 1947, and the first confirmed human infection was reported in Uganda between1962-1963. From its origin in East Africa, ZIKV then spread to West and Central Africa with a limited occurrence in North Africa. ZIKV has been circulating in Africa for over 60 years, but less attention had been given, not until its recent outbreaks outside Africa and its discovered association with adverse congenital disabilities. ZIKV is known to cause several debilitating neurological complications, including microcephaly in newborns and Guillain-Barré Syndrome (GBS) in adults.
This review thus aims to highlight the epidemiological evidence and distribution of ZIKV in Africa with a focus on determinants, complications as well as management. We used literature searched from key databases such as Google Scholar, Web of Science, among others, to collect relevant current information about ZIKV in Africa.
Climate, sociodemographic factors, and increasing human density impact the spread of ZIKV in Africa, as in other areas. Furthermore, ZIKV transmission is affected by several unique factors, including the potential risk of sexual transmission, as well as vast numbers of refugees and other travellers from ZIKA endemic areas across Africa, and all over the world.
The review identifies the need to improve surveillance mechanisms and focusing on vector control as critical steps to enable prompt detection and avert potential outbreaks of the disease in the continent.
5 citations
Cites background from "Pathogenesis, diagnostic challenges..."
...It is an icosahedral, enveloped, non segmented, positivesense, singlestranded RNA virus which has a diameter of 40nm, with an outer coating and dense inner core [58]....
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...production of modified viral polyprotein followed by the collection of the immature virions in secretory vesicles and endoplasmic reticulum before being released [58,59]....
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TL;DR: This short review summarizes the insights of ZikV infection, present status of the disease in Bangladesh and its neighboring countries, and recommendations for necessary preparations and strategies to be taken for effective controlling of the ZIKV infection in Bangladesh before getting any havoc.
Abstract: Zika virus, a member of Flaviviridae is the etiology of Zika or Zika fever or Zika virus (ZIKV) disease characterized by mild symptoms similar to very mild form of Dengue or Chikungunya. The virus transmits through Aedes mosquitoes, particularly by Aedes aegypti. The most dangerous effect of ZIKV infection is the ability of the virus to cause microcephaly and congenital malformation to the newborn baby if the mother is infected. The neurological disorders including Guillain-Barre syndrome might be associated with adults and children due to ZIKV infections. Zika has emerged as a serious global public health problem as it has been found in 87 countries, particularly in Africa, America, and Asia and has no vaccine and treatment so far. Bangladesh is at a high risk of ZIKV infection and we consider ZIKV as a possible emerging threat for Bangladesh. This short review summarizes the insights of ZIKV infection, present status of the disease in Bangladesh and its neighboring countries, and recommendations for necessary preparations and strategies to be taken for effective controlling of the ZIKV infection in Bangladesh before getting any havoc.
3 citations
Cites background from "Pathogenesis, diagnostic challenges..."
...So far, there is no preventive vaccines and medicines against ZIKV infection [7]....
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