In Focus: Zika virus 2018
The accelerated geographical spread of Zika infection in 2015-2016 and the epidemic peak has passed, however, lessons learned and persisting medical consequences indicate, similar threats triggered by viruses of high variation and with speedy life-cycle can evolve anywhere, anytime.
At present, there are no authorized anti-Zika chemotherapy or vaccine. Epidemiological, experimental and clinical efforts of 2016 and 2017 expectedly provide 2018 with definite potential of getting closer to preventive and protective defense against Zika - and other pathogenic - viral infections, in practice. Vaccine development seems to be the flagship towards this strategic purpose. However, as for the experimental results published in 2016, a new trend is on way, the repurposed use of authorized antiviral drugs in anti-Zika monotherapy or combination therapy. When protecting against Zika viral infection the turn to chemotherapy may give more time to developing an adequate vaccine. However, vaccine development faces the pivotal question of safety when dealing with beneficial or disabling effects of anamnestic immune conditions generated from preceding flavivirus infection(s) or former vaccination(s).
Whether vaccine or chemotherapy is the future solution, early and reliable diagnostics for effective therapy are indispensable. Today, the two techniques enjoying international acception and recommendation for Zika Diagnostics are the detection of virus RNA by PCR based nucleic acid tests and the serological detection of Zika-specific IgM antibody with MAC-ELISA test. Besides their advantages, both techniques raise some issue in diagnostic reliability. For example, the PCR-based nucleic acid test may give false negative results in blood and urine samples since Zika-RNA detection is optimal at ≤ 7 days after onset of infection symptoms (nota bene, Zika infections are often asymptomatic). Later on, the diagnostic window turns to narrow due to significant fall in viremia. The serological detection of IgM antibody (> 7 days after onset of infection symptoms) may manifest in "crosstalk", i.e. a cross-reactivity with non-Zika Flavivirus infection (e.g. cross-reaction between Dengue-specific and Zika-specific antibodies in the acute phase of infection due to similarities in spatial structure and sequences of Dengue 'E' and Zika 'E' antigens), rendering thus the method unreliable especially in areas where Dengue and Zika co-circulate..
Thus the rolled on question remains: what technical solutions reach the pipeline for reliable Zika diagnostics?
The terrestrial distribution and the incidence of congenital abnormalities are covered by the Brazilian study of suspected infectious diseases registered in S„o Paulo Member State (248,221,996 km≤ with about 44,749,699 inhabitants) during the period 30 October 2015 to 30 June 2017.
The ratios were as follow: out of 1151 cases, Martins et al. processed 960 cases, of which 486 (50.6%) analysis and follow-up were abolished (141/486 cases did not meet the specifications, in 345/486 cases fetal neuronal development went normal). Thus, 960-486 = 474 cases of suspected infection were investigated including the 244 (51.5%) proven cases of embryonic abnormalities of non-infection origin.
In the further 230/474 cases (48.5%) congenital infection syndrome was presumed. The latter presumption was proved in 146/230 (63.5%) cases: of them 87 cases (37.8%) were subjected to laboratory diagnostic tests (RT-PCR) and 59 (25.7%) to imaging processes when following maldevelopment.
Zika virus was detected in 55 infected individuals of the laboratory confirmed 87 cases (the remaining 32/87 individuals were positive for syphilis, cytomegalovirus, toxoplasmosis, herpes simplex virus, Coxsackie virus, parvovirus).
The Zika-positive 55 cases are: 23 newborns among them 17 with microcephaly /// 22 abortions /// 5 fetuses with central nervous system anomalies /// 3 newborn early deaths /// 2 stillborn infants.
From an epidemiological point of view, the report emphasizes the need for complete information on public health registers, the availability of clinical specimens required to detect Zika virus (and other infective agents ...), the selective specificity of nucleic acid based laboratory tests to detect viruses, and liable laboratory tests (STORCH) to exclude the interference of other infectious agents.
... and the question remains:
Zika neurotropism: what is going on there?
Zika virus contra immune system elements: what is going on there?