In some patients (such as patients 4, 5, 10, 16, 53), high IgM ratios during the acute phase were associated with delayed and moderate increases in Zika virus IgG ratios, possibly reflecting a primary flavivirus or Zika virus infection; for other patients (such as patients 20, 34, 41, 58, 62), an early increase in the IgG ratio was combined with a low or even negative Zika virus IgM ratio throughout follow-up, indicating secondary flavivirus infections
. These 2 types of kinetics showed contrasted signal intensities, which are not observed with our in-house ELISA assays, in which whole Zika virus is used as an antigen (data not shown).
Lanciotti and coworkers (12) reported that ZIKV-infected patients had IgM antibodies against dengue viruses, especially if ZIKV was a secondary flavivirus infection
. Thus, in areas where other flavivirus infections
are prevalent, such as in the Americas, it is expected an extensive cross-reactivity between dengue and Zika IgM antibodies, which could lead to the misdiagnosis of these diseases (12).
TLR3 Plays Dual Functions during Flavivirus Infection
. TLR3 has been found on the endosome of cells and shares the same function both in mammals and avians, which recognizes double-stranded RNA (dsRNA) and induces type I IFN [43, 44].
Cross-reactions in serological diagnosis of flavivirus infections
. In: Petrovic T, editor.
However, in light of the limitations of serologic testing (e.g., cross-reactivity and false-positive test results), for pregnant women without a previous diagnosis of laboratory-confirmed Zika virus infection, including those with laboratory evidence of flavivirus infection
or laboratory evidence of presumptive Zika virus or flavivirus infection
(Table 1), decisions about testing during a subsequent pregnancy should be made using a shared patient-provider decision-making model.
Unknown also is the role of asymptomatic infection in the development of congenital infection or whether previous exposure to heterologous flavivirus infection
(e.g., DENV) enhances the severity of disease.
Excivion is a private UK company that has developed a proprietary antigen design platform for viral vaccines which it is applying to flavivirus infections
In fact, a complete loss-of-function mutation in CCR5 is associated with symptomatic neuroinflammatory disease for West Nile and tick-borne encephalitis flavivirus infections
Cross reactions with other flaviviruses interfere with serologic testing, particularly the ELISA for IgG and this affects the interpretation of test results in travellers exposed to other flavivirus infections
, including those previously vaccinated against flavivirus infections
, such as yellow fever and Japanese encephalitis .
WNV specific IgM and IgG capture ELISA tests and the Plaque Reduction Neutralization Test (PRNT) detecting WNV specific neutralizing antibodies in CSF and serum remains the assay required for confirmation of flavivirus infections
. MAC-ELISA test is the most efficient for detection of IgM antibody and is valuable for serosur-veillance.
Reactivity of serum samples from patients with Flavivirus infections
measured by immunefluorescense assay and ELISA.
As with most of the flavivirus infections
, serology is the most practical method of diagnosis, and virus isolation and RT-PCR have limited utility.
For assessing the true disease burden of flavivirus infections
, seroprevalence studies are effective.
Finally, published data from USZPR include many pregnancies with unspecified flavivirus infections
, and thus the estimates of the proportion with birth defects potentially related to Zika virus infection might underestimate the actual Zika impact, given that some included pregnant women likely had other flavivirus infections
, increasing the size of the denominator.